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Belarus turned Su-25 into nuclear bomb carriers. Just the plane is not fast enough for that?

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Belarus turned Su-25 into nuclear bomb carriers. Just the plane is not fast enough for that?

In a message posted on the Telegram social network, the Ministry of Defense of Belarus presented a video saying that its military pilots of Su-25s have completed additional training under the supervision of instructors from the Russian Federation in order to be able to use armaments of a “special designation”.

Su-25. Image credit: Air Force of Belarus

The video does not say precisely what kind of weapons they had in mind, but defense experts unanimously agree that “special designation” explicitly means nuclear weapon.

This course of action was expected since the meeting of Belarusian and Russian presidents in August 2022. Then, Belarusian President Aleksander Lukashenko disclosed that Russia has upgraded a certain number of jets from his country’s military fleet to enable them to carry tactical nuclear weapons.

The only serious technical issue is that the Su-25 attack aircraft is just a subsonic vehicle with velocities that are sub-optimal for the use of nuclear weapons.

 

Theoretically, Su-25 could deliver free-falling bombs from their maximum flight altitude, but with a substantial risk that the aircraft together with the pilot would be destroyed during the attack.

Previously, both Russian and Belarusian media assumed that this attack capability was reserved for the Su-24 bomber plane which was specially designed for this kind of tasks. But after the latest announcement, it became obvious that these will be Su-25s, not Su-24s.

The Su-25 was developed in the former USSR and even then it was out of the question that this aircraft could become a nuclear-capable carrier.

Su-24. These planes are much faster than Su-25.

Su-24. These planes are much faster than Su-25. Image credit: Armed Forces of Russia

The method for using nuclear munitions requires that the plane flies at a relatively low altitude at its maximum possible speed, drops the bomb, and withdraws in the opposite direction as fast as possible, to avoid being hit by a nuclear explosion.

For this purpose, the Soviet Union built Yak-28 bomber in the 1950s which had a maximum speed of 1830 km/h. Later it was replaced by Su-24 which could reach 1700 km/h, and even at low altitudes, it could fly at velocities up to 1400 km/h. Currently, the Russian Federation has Su-34 reaching 1400-1900 km/h depending on the flight altitude.

Meanwhile, the top speed of the Su-25 is does not exceed 1000 km/h.

PH-40 tactical nuclear bomb. It could fit on Su-25, but the plane still would not be able to lfy fast enough to escape its destruction.

PH-40 tactical nuclear bomb. It could fit on Su-25, but the plane still would not be able to lfy fast enough to escape its destruction.

From the structural perspective, Su-25 could take off the ground with a nuclear bomb onboard, such as 30-kiloton PH-40. But would it be able to escape safely after dropping it?

Defense Express notes that Su-25 which appeared in the Belarusian video was not covered in special light-colored “anti-atomic” coating which should protect the aircraft from light radiation during a nuclear explosion.

 


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Ireland, Community Sings “Bella Ciao Fiona” on a Good Friday fundraising

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Bella Ciao Fiona – Fabulous Charity Event Celebrates the Life and Legacy of Dancer and Artist Fiona Fennell

Dublin, WIRE / A night of musical theatre, dance and true community spirit under the title “Bella Ciao Fiona” celebrated the life and legacy of dancer and artist Fiona Fennell on Good Friday.

Fiona passed away unexpectedly on Valentine’s Day after a short battle with cancer, leaving behind her 17-year old son Kyle.

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Fiona’s sister together with Diana Stahl, Director Public Affairs of Scientology in Dublin

Fiona’s family decided to turn the tragic loss into a positive and beautiful creation, in true Fiona style. The fаmily teamed up with volunteers from the Scientology Community Centre in Firhouse, Dublin and with 6 performing arts and stage schools to put on an upbeat variety show in honour of Fiona and her lifetime dedicated to the arts.

The event saw a lot of community support and raised over 8,000 Euros to help Kyle who is getting settled in a cabin which is being built in the garden of his aunt Nicola.

This comes, in addition, to support for the construction of the cabin via GoFundMe that so far has amounted to 31,260 Euros.

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Ireland, Community Sings “Bella Ciao Fiona” on a Good Friday fundraising 17

The stage on the night saw passionate performances by Attitude Dance and Stage School which is run by Fiona’s cousin Aishling Fennell who was also the creative director of the entire show; as well as by Spotlight Theatre Group; Steptacular School of Performing Arts; KNC Performing Arts; Confidance Performing Arts and The Helen Jordan Stage School, where Fiona herself had been a student.

The night was hosted by the truly magnificent Rob Murphy, who kept the audience laughing from start to finish.

The grand finale of the show was Fiona’s own time on stage – with her tap dancing shoes in the spotlight and a video edit of Fiona’s many performances throughout the years playing on the screens, the audience applauded and sang along “Bella Ciao” – an Italian upbeat song Fiona had wished to be played for those who wanted to say goodbye.

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Ireland, Community Sings “Bella Ciao Fiona” on a Good Friday fundraising 18

The show ended with a standing ovation for Fiona and the announcement that Fiona’s family and the team at the Scientology Community Centre will from now on hold the Bella Ciao Fiona charity event every year on Good Friday, in memory of Fiona and as part of her legacy to the world.

A cause or a family in need will be chosen every year and all proceeds from the event will go to support them.

The first Bella Ciao Fiona charity fundraiser was not only a great success but a true statement of the power the community has when it gets together to help and to heal.

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Ireland, Community Sings “Bella Ciao Fiona” on a Good Friday fundraising 19

Why this Russian T-90A main battle tank appeared in the United States?

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Why this Russian T-90A main battle tank appeared in the United States?

The Russian T-90A main battle tank that was spotted in Louisiana sparked lots of heated debates and discussions about the reason why and also how this machine appeared in the United States.

Russian main battle tank T-90A on a trailer in the United States. Image credit: Special Kherson Cat via Twitter

The images circulating on social networks were taken quite freshly. But the tank itself was apparently captured by Ukraine last year, writes The Drive.

The fact of the tank’s capture by the Ukrainian Armed Forces was confirmed by the open source intelligence (OSINT) trackers. The trailer carrying this vehicle was photographed at a truck stop on the southernmost cross-country highway Interstate 10.

The T-90A is considered one of the most modern Russian combat machines among those used during their invasion of Ukraine. As with all tanks, it is also exceptionally heavy – according to the publication, the truck that was hauling this huge load experienced problems with its transmission.

The tank itself does not contain its full equipment and add-on systems – for example, its machine guns and fire control systems have been removed. However, some explosive reactive armor containers have been left on the gun turret.

The exact reason why T-90A appears in the United States remains unknown. The experts, however, say that the U.S. Military may have brought this tank to the United States to thoroughly analyze its features in order to gain insights into its capabilities and potential vulnerabilities.

We could expect that later the results of this analysis could be handed over to Ukrainian defenders in order to improve their defensive capabilities against this machine and similar military equipment.

Oryx, an open source intelligence community, reports that the Ukrainian Army has captured at least 549 Russian tanks to this date, not counting those units that were destroyed in combat.


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‘It can happen anywhere’: General Assembly reflects on Rwandan genocide

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‘It can happen anywhere’: General Assembly reflects on Rwandan genocide

“We are together to mourn the more than one million children, women, and men who perished in 100 days of horror 29 years ago,” said UN Secretary-General António Guterres.

“We pay tribute to the resilience of the survivors [and] recognize the journey of the Rwandan people towards healing, restoration, and reconciliation. And we remember – with shame – the failure of the international community. The failure to listen and the failure to act.”

In April 1994, decades-long intercommunal tensions and clashes unfolded before the world’s eyes into genocide, as Hutu leaders led a deadly campaign against the Tutsi. The bloodshed unfolded, despite the presence of the UN Assistance Mission for Rwanda and despite the General Assembly’s unanimous adoption of the Genocide Convention in 1948, which defines genocide as a crime under international law.

“The killings did not start spontaneously,” Mr. Guterres said. “They were carefully planned long in advance and executed deliberately and systematically; it was premeditated murder in broad daylight.”

A generation since the genocide, “we must never forget the dangers posed by the fragility of civility in all societies; it precedes and promotes violence”, he cautioned.

‘Megaphones of hate’ grow bigger today

The hate and propaganda that paved the path to genocide in Rwanda was broadcast on TV, printed in newspapers, and blasted over radio, he said.

“Today, the megaphones of hate are even bigger,” he said, noting that across the internet, incitement to violence, vicious lies and conspiracies, genocide denial and distortion, and the demonization of “the other”, proliferate with little to no checks.

Calling for stronger guardrails, clearer responsibilities, and greater transparency in the digital world, he said the launch of the UN Strategy and Plan of Action on Hate Speech provides a framework for support to countries to counter this scourge while respecting freedom of expression and opinion.

“Today, I call on all Member States to become parties to the Convention on the Prevention and Punishment of the Crime of Genocide without delay, and I call on all States to back their commitments with action,” the UN chief said.

“Together, let us stand firm against rising intolerance,” he added. “Let us truly honour the memory of all Rwandans who perished by building a future of dignity, security, justice, and human rights for all.”

Rwandan genocide was ‘not an accident’

General Assembly President Csaba Kőrösi said the genocide was not an accident, but rather, it stemmed from years of fomenting a racist ideology and waging a campaign aimed at the systematic destruction of a population. As it was carried out, the world was silent.

“We were silent despite repeated and unmistakable early warnings about the preparation of genocide,” he said. “To this unconscionable inaction, we must say ‘never again’.”

With strength and determination, the people of Rwanda have rebuilt their nation from the ashes of devastation. Today, the success of these endeavours is seen everywhere, he said, pointing to gender parity in the lower house of Parliament, the vibrancy of Rwandan innovation, the resilience of its economy, and in the strength of its health care system.

“Importantly, Rwanda has invested in its young people, opening opportunities for those under 20 years old – who represent half of its dynamic population,” he said. “Rwandans have built a nation that looks towards a better future. May we in the General Assembly do the same.”

‘They killed my entire family’

The Assembly also heard from genocide survivors, who shared their harrowing stories.

Ahead of the event, Henriette Mutegwaraba, 50, a survivor who now lives in the United States, met with UN News to discuss how she survived and healed, and how hate speech today strikes a haunting echo of the genocide in Rwanda.

“Every time I talk about it, I cry,” she said. “They raped women. They opened pregnant women; opened their wombs with a knife. They put people in septic holes alive. They killed our animals. They destroyed our homes. They killed my entire family, my mom, my four siblings.”

During the 1994 genocide against Tutsi, “the whole world turned a blind eye”, she said. “They knew. Nobody came to help us. Nobody came to us. I hope that this will never happen to anybody in this world. I hope that the UN can come up with a way to respond quickly.”

‘Genocide can happen anywhere’

Nobody is immune to what happened to Rwanda in 1994, she said, emphasizing that there is so much propaganda happening in the United States and people are not paying attention and the country is very divided.

Ms. Mutegwaraba elaborated on this current issue in her book By Any Means Necessary. Indeed, she said she had felt the same fear on 6 January 2021 during the attack on the United States capitol that she did in April 1994.

Genocide can happen anywhere,” she said. “Do we see the signs? Yes, we see the signs. Do we pretend that it doesn’t affect us or our world? Yes, we do. My message is this: wake up. Something’s happening. It’s all about propaganda.”

 

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Haiti: $720 million plan to support millions facing gangs, hunger and cholera

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Haiti: 0 million plan to support millions facing gangs, hunger and cholera

The 2023 funding appeal is the largest for the Caribbean country since the devastating 2010 earthquake and more than double the amount requested last year. 

The UN humanitarian affairs office (OCHA) said the number of Haitians who require aid to survive doubled over the past five years to 5.2 million, and the aim is to reach 60 per cent, or 3.2 million people. 

‘A critical time’ 

The full 2023 Humanitarian Response Plan, which will be launched on 19 April, comes at “a critical time”, said Ulrika Richardson, UN Humanitarian Coordinator in Haiti. 

“With the situation in the country rapidly deteriorating, this year’s plan will address the most immediate humanitarian and protection needs while strengthening people’s and institution’s resilience to natural shocks,” she said. 

“At the same time, what the people of Haiti desperately want is peace and security, and we should all support efforts to that end.”  

Climate of fear 

A key driver of the crisis is gang violence, which continues to spread across the country, OCHA said. An estimated 80 per cent of the metropolitan area of the capital, Port-au-Prince, is either under the control or the influence of gangs.  

“There is a constant climate of fear, especially in Port-au-Prince,” Ms. Richardson said. “Haitians put their lives at risk simply by trying to go to work, feed their families, or take their children to school.”  

Armed violence disproportionately impacts women and girls, but boys are also affected, OCHA reported. 

Rape, including gang rape, and other forms of sexual violence, is being used to terrorize the population, including children as young as age 10, the UN agency said. Meanwhile, many gangs also recruit children into their ranks.  

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Chad: aid for displaced desperately needed to avoid hunger

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Chad: aid for displaced desperately needed to avoid hunger

Speaking from Ndjamena, Pierre Honnorat, director of the UN World Food Programme (WFP) in Chad, said that as the country moves into the lean season in-between harvests, food assistance could grind to a complete halt.

“Chad is surrounded by countries with crises and hosting some 600,000 refugees from Sudan, Niger, Cameroon and Central African Republic. It’s one of the biggest caseloads in Africa. And the number kept rising with the recent conflict in the communities in Sudan,” Mr. Honnorat told reporters in Geneva.

An additional 300,000 people in need of aid are internally displaced Chadians.

Complex crisis, chronic underfunding

WFP said that after fleeing conflict and violence, refugees, internally displaced people and their host communities face growing food insecurity and malnutrition, high food prices and the destructive effects of climate change. In the second half of 2022, the country saw the most devastating floods in 30 years.

Mr. Honnorat flagged that last year, some 90 per cent of refugees in Chad did not receive adequate food assistance and rations had to be cut in half.

He warned that “2023 is another very difficult year, whereby we have absolutely no funding from May onwards for the refugees and the displaced people.”

Food assistance coming to a halt

WFP has already reduced its support in April and will only be able to serve just over 270,000 refugees this month.

To avoid food assistance coming to a complete halt and to “put food on the table of all crisis-affected populations” in Chad, WFP urgently needs additional funding of $142.7 million for the coming six months.

Hunger compounding vulnerabilities

Mr. Honnorat called on donors to help the Government of Chad “in their efforts to host so many refugees with so many crises at the same time”, while emphasizing the upcoming “very difficult” lean season.

WFP projects that nearly 1.9 million people will be in severe food insecurity from June to August 2023, while more than 1.3 million children will suffer from acute malnutrition.

According to the UN agency, other disastrous impacts of the crisis could include a rise in child labour, under-aged marriage and recruitment into armed groups.

UNHCR appeal

Echoing the call for urgent action, Matthew Saltmarsh from the UN refugee agency, UNHCR, also appealed to the international community to help tackle the crisis.

“For our part of the appeal, we’re looking to raise $172.5 million to provide protection and relief assistance to the one million forcibly displaced people and their hosts”, he said, adding that UNHCR’s appeal was, for now, only 15 per cent funded.

Development solutions

Speaking about longer-term solutions to the crisis, including development interventions, Mr. Honnorat highlighted a new project which WFP was running together with UNHCR and the Chadian agriculture ministry, to promote empowerment and self-reliance among the displaced by enabling them to become farmers and live off the land.

“We have just rehabilitated 1,600 hectares of land, which have already produced 2,900 tonnes of food”, he said, stressing that the return on investment of the operation is “fantastic” and that most importantly, 16 villages now no longer require assistance.  

Mr. Honnorat went on to underscore that in his 33 years at WFP, he had rarely seen development projects as “solid” as in Chad and praised the efforts of the Government in favour of the refugees, including ongoing work on a new asylum law, which should be finalized soon.

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Yemen: UN envoy welcomes mass prisoner release, urges push for political solution to war

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Yemen: UN envoy welcomes mass prisoner release, urges push for political solution to war

“Nearly 900 conflict-related detainees are being released by the parties in Yemen starting today, Friday, and over the course of three days,” the Office of the Special Envoy of the Secretary-General for Yemen said in a statement.

“This release operation comes at a time of hope for Yemen as a reminder that constructive dialogue and mutual compromises are powerful tools capable of achieving great outcomes,” Mr. Grundberg’s office added.

 

Swiss connection

The development is in line with an agreement reached by the Supervisory Committee on the Detainees’ Exchange Agreement, which announced the initiative at UN Geneva in March.

Facilitated by Special Envoy Grundberg and the International Committee of the Red Cross, the agreement involves the freeing of 887 conflict-related detainees, held over the course of more than eight years of clashes between Yemen’s Government and Houthi opposition fighters that are widely believed to have killed thousands and created what the UN has described as the worst humanitarian emergency in the world.

“More releases” are planned once Yemen’s warring parties meet in May, according to the Special Envoy’s Office, which noted that the Red Cross is managing the release operation which includes flights between six airports in Yemen and Saudi Arabia to repatriate all prisoners.

 

Ramadan cheer

“Today, hundreds of Yemeni families get to celebrate Eid with their loved ones because the parties negotiated and reached an agreement. I hope this spirit is reflected in ongoing efforts to advance a comprehensive political solution,” said Special Envoy Grundberg.

After highlighting that “thousands more families are still waiting to be reunited with their loved ones”, the UN official expressed hope that the warring parties would “build on the success of this operation to fulfill the commitment they made to the Yemeni people” in talks in Sweden in 2018, “to release all conflict-related detainees and bring this suffering to an end”.

Apart from carrying out prisoner exchanges, the two other main components of the Stockholm Agreement – endorsed by the UN Security Council under resolution 2451 (2018) – covered an agreement on the city of Hudaydah; the ports of Hudaydah, Salif and Ras Issa, and “a statement of understanding” on the city of Taiz.

In his statement, Special Envoy Grundberg also urged the parties “to immediately and unconditionally release all arbitrarily detained individuals and to adhere to international legal standards” regarding detention and fair trials.

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AI Tool Predicts Colon Cancer Survival, Treatment Response

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AI Tool Predicts Colon Cancer Survival, Treatment Response

Model offers actionable insights for physicians, could augment clinical decisions in resource-limited areas.

DNA Genotyping and Sequencing. A technician washes arrays used in genome-wide association studies (GWAS). Illustrative photo. Image credit: NCI

A new artificial intelligence model designed by researchers at Harvard Medical School and National Cheng Kung University in Taiwan could bring much-needed clarity to doctors delivering prognoses and deciding on treatments for patients with colorectal cancer, the second deadliest cancer worldwide.

Solely by looking at images of tumor samples — microscopic depictions of cancer cells — the new tool accurately predicts how aggressive a colorectal tumor is, how likely the patient is to survive with and without disease recurrence, and what the optimal therapy might be for them.

Having a tool that answers such questions could help clinicians and patients navigate this wily disease, which often behaves differently even among people with similar disease profiles who receive the same treatment — and could ultimately spare some of the 1 million lives that colorectal cancer claims every year.

A report on the team’s work is published in Nature Communications.

The researchers say that the tool is meant to enhance, not replace, human expertise.

“Our model performs tasks that human pathologists cannot do based on image viewing alone,” said study co-senior author Kun-Hsing Yu, assistant professor of biomedical informatics in the Blavatnik Institute at HMS. Yu led an international team of pathologists, oncologists, biomedical informaticians, and computer scientists.

“What we anticipate is not a replacement of human pathology expertise, but augmentation of what human pathologists can do,” Yu added. “We fully expect that this approach will augment the current clinical practice of cancer management.”

The researchers caution that any individual patient’s prognosis depends on multiple factors and that no model can perfectly predict any given patient’s survival. However, they add, the new model could be useful in guiding clinicians to follow up more closely, consider more aggressive treatments, or recommend clinical trials testing experimental therapies if their patients have worse predicted prognoses based on the tool’s assessment.

The tool could be particularly useful in resource-limited areas both in this country and around the world where advanced pathology and tumor genetic sequencing may not be readily available, the researchers noted.

The new tool goes beyond many current AI tools, which primarily perform tasks that replicate or optimize human expertise. The new tool, by comparison, detects and interprets visual patterns on microscopy images that are indiscernible to the human eye.

The tool, called MOMA (for Multi-omics Multi-cohort Assessment) is freely available to researchers and clinicians.

Extensive training and testing

The model was trained on information obtained from nearly 2,000 patients with colorectal cancer from diverse national patient cohorts that together include more than 450,000 participants — the Health Professionals Follow-up Study, the Nurses’ Health Study, the Cancer Genome Atlas Program, and the NIH’s PLCO (Prostate, Lung, Colorectal and Ovarian) Cancer Screening Trial.

During the training phase, the researchers fed the model information about the patients’ age, sex, cancer stage, and outcomes. They also gave it information about the tumors’ genomic, epigenetic, protein, and metabolic profiles.

Then the researchers showed the model pathology images of tumor samples and asked it to look for visual markers related to tumor types, genetic mutations, epigenetic alterations, disease progression, and patient survival.

The researchers then tested how the model might perform in “the real world” by feeding it a set of images it had not seen before of tumor samples from different patients. They compared its performance with the actual patient outcomes and other available clinical information.

The model accurately predicted the patients’ overall survival following diagnosis, as well as how many of those years would be cancer-free.

The tool also accurately predicted how an individual patient might respond to different therapies, based on whether the patient’s tumor harbored specific genetic mutations that rendered the cancer more or less prone to progression or spread.

In both of those areas the tool outperformed human pathologists as well as current AI models.

The researchers said the model will undergo periodic upgrading as science evolves and new data emerge.

“It is critical that with any AI model, we continuously monitor its behavior and performance because we may see shifts in the distributions of disease burden or new environmental toxins that contribute to cancer development,” Yu said. “It’s important to augment the model with new and more data as they come along so that its performance never lags behind.”

Discerning telltale patterns

The new model takes advantage of recent advances in tumor imaging techniques that offer unprecedented levels of detail, which nonetheless remain indiscernible to human evaluators. Based on these details, the model successfully identified indicators of how aggressive a tumor was and how likely it was to behave in response to a particular treatment.

Based on an image alone, the model also pinpointed characteristics associated with the presence or absence of specific genetic mutations — something that typically requires genomic sequencing of the tumor. Sequencing can be time-consuming and costly, particularly for hospitals where such services are not routinely available.

It is precisely in such situations that the model could provide timely decision support for treatment choice in resource-limited settings or in situations where there is no tumor tissue available for genetic sequencing, the researchers said.

The researchers said that before deploying the model for use in clinics and hospitals, it should be tested in a prospective, randomized trial that assesses the tool’s performance in actual patients over time after initial diagnosis. Such a study would provide the gold-standard demonstration of the model’s capabilities, Yu said, by directly comparing the tool’s real-life performance using images alone with that of human clinicians who use knowledge and test results that the model does not have access to.

Another strength of the model, the researchers said, is its transparent reasoning. If a clinician using the model asks why it made a given prediction, the tool would be able to explain its reasoning and the variables it used.

This feature is important for increasing clinicians’ confidence in the AI models they use, Yu said.

Gauging disease progression, optimal treatment

The model accurately pinpointed image characteristics related to differences in survival.

For example, it identified three image features that portended worse outcomes:

  • Greater cell density within a tumor.
  • The presence of connective supportive tissue around tumor cells, known as stroma.
  • Interactions of tumor cells with smooth muscle cells.

The model also identified patterns within the tumor stroma that indicated which patients were more likely to live longer without cancer recurrence.

The tool also accurately predicted which patients would benefit from a class of cancer treatments known as immune checkpoint inhibitors. While these therapies work in many patients with colon cancer, some experience no measurable benefit and have serious side effects. The model could thus help clinicians tailor treatment and spare patients who wouldn’t benefit, Yu said.

The model also successfully detected epigenetic changes associated with colorectal cancer. These changes — which occur when molecules known as methyl groups attach to DNA and alter how that DNA behaves — are known to silence genes that suppress tumors, causing the cancers to grow rapidly. The model’s ability to identify these changes marks another way it can inform treatment choice and prognosis.


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Untangling the Mystery of Sleep: Unexpected Connections Between the Brain and Gut

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Untangling the Mystery of Sleep: Unexpected Connections Between the Brain and Gut

Recent sleep research reveals unexpected connections between the brain and gut.

Sleep is one of the essential human activities — so essential, in fact, that if we don’t get enough sleep for even one night, we may struggle to think, react, and otherwise make it through the day. Yet, despite its importance for function and survival, scientists still don’t fully understand how sleep works.

Sleeping kitten – illustrative photo. Image credit: Kate Stone Matheson via Unsplash, free license

Enter Dragana Rogulja, a neurobiologist on a quest to unravel the basic biology of sleep.

As a self-described latecomer to science, Rogulja was drawn to questions she considers “broadly interesting and easy to understand on a basic human level.”

One of these questions is what happens when we sleep.

For Rogulja, an associate professor of neurobiology at the Blavatnik Institute at Harvard Medical School, an intriguing aspect of sleep is the loss of consciousness and awareness it brings as the outside world disappears and the inner world takes over.

In a conversation with Harvard Medicine News, Rogulja delved into the details of her sleep research, which uses fruit flies and mice to explore why we need to sleep and how we disconnect from the world during sleep.

An experimental setup that the Rogulja lab uses to monitor the activity and health of fruit flies. The flies are separated into individual tubes, and their movements are captured by infrared beams. In a 2020 study, the researchers found that the more sleep flies lost, the shorter their lifespans became. Image credit: Rogulja lab.

Harvard Medicine News: What are you studying in the context of sleep?

Rogulja: There are two main questions that my lab has been pursuing for the past several years. The first is why sleep is necessary for survival. Why is it that if you don’t sleep, you will literally die after not too long? The other question is how your brain disconnects from the environment when you fall asleep. How are stimuli prevented from reaching your brain during sleep?

Elevating the threshold for sensory arousal is essential for sleep, and we want to understand how that barrier is built around the brain. Sleep is one unified state, but it seems to have multiple components that are regulated through separate mechanisms. We want to understand those mechanisms.

HMNews: How has your research changed how you think about sleep?

Rogulja: For a long time, scientists have been guided by the principle that sleep is of the brain, by the brain, and for the brain. As a result, research has largely focused on the brain regarding why sleep is necessary for survival.

However, we now realize that while sleep may be for the brain, it’s not just for the brain. Sleep is a super old behavior that originated in the earliest animals. These animals had no brain and only a very simple nervous system.

Then, as animals became more complex, these brain-related purposes of sleep evolved. However, researchers have looked at the brains of sleep-deprived animals to try to find a reason why they die, and they haven’t found anything. On the other hand, clinical data show that sleep deprivation in humans leads to all kinds of diseases in the body. To us, this really suggested that sleep is about more than just the brain.

Our research tells us that we need to stop thinking about the brain separately from the body when it comes to sleep. I’m still shocked by how neuroscientists think about the brain as having superiority over the body and being at the top of a hierarchy.

To solve the biggest mysteries in neuroscience, we need to take a more integrated approach, which is what my lab is trying to do for sleep. We have found that we really need to think about the whole body to understand sleep. And it makes sense. When you go to sleep, your muscles relax, your circulation changes. Of course, it’s about the whole body.

HMNews: What tools do you use to study sleep?

Rogulja: Historically, a lot of sleep research has been done on humans, but those experiments tend to be limited and descriptive, because you can’t really do experimentation on humans.

However, over the last two and a half decades, scientists have realized that fruit flies sleep; more recently, we figured out that the genes that regulate sleep in flies are conserved in mice.

When I started my lab, we were only using fruit flies as a model system to study sleep, but we have since established a mouse model as well. Fruit flies allow us to test a lot of hypotheses quickly and do large, unbiased genetic screens, and then we can test what we find out in flies in mice, which, as mammals, are more similar to humans.

HMNews: In your 2020 Cell paper, you tackled why sleep is necessary for survival. What’s the answer?

We found that fruit flies who slept less had shorter lifespans: We saw a correlation where the more sleep the flies lost, the faster they died. Interestingly, the mode of sleep deprivation did not matter. What mattered was the amount of sleep lost.

There seemed to be an inflection point where sleep loss was associated with death, which told us that something specific might be happening in the body instead of general wear and tear.

To investigate this further, we stained different organs in sleep-deprived flies with markers of cell damage. We found that in the gut, there was an increase in oxidizing molecules, and the peak of oxidation correlated with the inflection point where the flies started to die.

We confirmed this finding in sleep-deprived mice. But when we gave sleep-deprived flies antioxidants or turned on antioxidant-producing genes in the gut, we found the flies could survive on little or no sleep, suggesting that the gut is a really important target of sleep.

HMNews: Are there any possible applications for humans?

Our findings suggest that if we can prevent oxidation in the gut, we might be able to counteract the effect of losing sleep. This is important because a lot of diseases are tied to gut dysfunction, and many diseases that arise when you don’t sleep enough may actually be a consequence of gut damage.

We’re now starting to think about how to diagnose gut oxidation due to lack of sleep in humans. We want to design “swallowables” — pills or tablets you could swallow that report the oxidative state of your gut by, for example, changing the color of your feces.

We’re also looking for biomarkers: molecules already circulating in the body that indicate lack of sleep and gut oxidation. My lab’s physicians are profiling sleep-deprived mice to look for such biomarkers.

We already have some molecules that are promising markers for oxidation and seem to decrease with antioxidant treatments. Eventually, it may be possible to design supplements that could be taken orally to reverse gut oxidation due to lack of sleep.

HMNews: You just published a new paper in Cell that explores how the brain disconnects from the environment during sleep. Tell us more.

Until now, we knew almost nothing about this. It wasn’t clear if there is a single place in the brain where all sensory information is attenuated during sleep, or if there are multiple such places. For example, are touch and temperature processed the same way during sleep?

Iris Titos, a postdoctoral researcher in my lab, built a system that can deliver mild, medium, or high levels of vibration to fruit flies. Typically, very few flies wake up when you use low-intensity vibrations, and when you use high-intensity vibrations, almost all the flies react.

Then, we did a large-scale screen to identify genes that control how easily flies wake up — so genes that make flies super easy to wake up, and genes that allow flies to sleep through an earthquake.

HMNews: What did the genetic screen show?

The results of the screen were very interesting. We identified a gene that codes for a molecule called CCHa1. When we depleted CCHa1 in the flies, they woke up very easily — so instead of 20 percent waking up at a particular level of vibration, 90 percent woke up.

However, while CCHa1 is present in both the nervous system and the gut, it was only when we depleted it in the gut that flies were roused more easily.

The cells in the gut that produce CCHa1 are called enteroendocrine cells, and they actually share many characteristics with neurons and can even connect and communicate with neurons. These cells face the inside of the gut, and they sort of “taste” the contents of the gut.

We found that the higher concentration of protein in the diet, the more CCHa1 these gut cells produced. This molecule then travels from the gut to the brain, where it signals to a small group of dopaminergic neurons that also receive information about vibrations.

These neurons produce dopamine, which usually promotes arousal, but in this case suppresses arousal. Vibrations weaken the activity of the dopaminergic neurons, which causes the flies to wake up more easily. CCHa1 produced by the gut essentially buffers the dopaminergic neurons against vibrations, allowing the flies to ignore the environment to a greater degree and sleep more deeply.

We also found that the CCHa1 pathway, while critical for gating mechanosensory information, has no influence on how easily the flies wake up when exposed to heat, suggesting that different sensory modalities such as vibration and temperature can be gated independently.

Finally, we showed that a higher protein diet also improved the quality of sleep in mice, making them more resistant to mechanical disturbances. We are now testing whether a similar signaling pathway is involved in mice.

HMNewsWhat do these findings tell you?

Well, we know from other research that when animals are starving, they suppress sleep in order to forage. By contrast, when they’re satiated, and especially when they’re satiated with proteins, they tend to sleep more.

Now, we’ve shown that animals sleep more deeply and become less responsive when there’s more protein in the diet. This suggests that if animals don’t need to look for food, they can disconnect from the environment and hide somewhere to sleep, which might be safer.

More broadly, our study implies that dietary choices impact sleep quality. Now we can explore this connection in humans to understand how diet could be manipulated to improve sleep.

HMNews: Is there anything about sleep that you think people often misunderstand?

Rogulja: I think people should be aware that how we feel and what’s going on in our bodies don’t have to be the same. In our research, we found that it’s possible to separate the feeling of sleepiness from the need to sleep — some sleep-deprived animals didn’t necessarily feel sleepy, which we could tell because they didn’t sleep extra to catch up on sleep after the deprivation stopped, but these animals still died from the lack of sleep.

This means that even if we can trick ourselves into not feeling sleepy, the lack of sleep still has negative effects on our bodies — for example, if you take a substance that makes you feel awake, the same amount of oxidation is going to happen in your gut.

People may say they’re OK with only a few hours of sleep a night, but they just mean they can make it through the day. Their bodies are still going to register the lack of sleep. We really cannot tell what’s happening in our bodies as a result of sleep deprivation, and we probably need more sleep than we think we do.

Source: HMS


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Mind Reader: Using AI to Decode Human Intelligence

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Mind Reader: Using AI to Decode Human Intelligence

The brain is a wonderful, mysterious thing: three pounds of soft gelatinous tissue through which we interact with the world, generate ideas and construct meaning and representation. Understanding where and how this happens has long been among neuroscience’s fundamental goals.

Reading mind – artistic interpretation. Image credit: Matt Perko/UCSB

In recent years researchers have turned to artificial intelligence to make sense of brain activity as measured by fMRI, turning AI models on the data to understand, with increasing specificity, what people are thinking and what those thoughts look like in their brains.

An interdisciplinary team at UC Santa Barbara pushes those boundaries by applying deep learning to fMRI data to create complex reconstructions of what the study subjects saw.

“There are several projects that try to translate fMRI signals into images, mostly because neuroscientists want to understand how brains process visual information,” said Sikun Lin, the lead author of a paper that appeared in a recent NeurIPS conference in November 2022.

According to Lin, UCSB computer science professor Ambuj Singh and cognitive neuroscientist Thomas Sprague, the resulting images generated by this study are both photorealistic and accurately reflect the original “ground truth” images. They noted that previous reconstructions didn’t create images with the same level of fidelity.

Key to their approach is that in addition to images, a layer of information is added through textual descriptions, a move that Lin said was made to add data to train their deep learning model.

Building on a publicly available dataset, they used CLIP (Contrastive Language-Image Pre-training) to encode objective, high-quality text descriptions that pair with the observed images, and then mapped the fMRI data of those observed images on to the CLIP space.

From there they used the output from the mapping models as conditions to train a generative model to reconstruct the image. The resulting reconstructions came remarkably close to the original images viewed by the subjects — closer, in fact, than any previous attempt to reconstruct images from fMRI data. Studies that have followed, including a notable one from Japan, have outlined methods for efficiently manipulating limited data into clear images.

“One of the main gists of this paper is that visual processes are inherently semantic,” Lin said. According to the paper, “the brain is naturally multimodal,” we use multiple modes of information at different levels to gain meaning from a visual scene, such as what is salient, or the relationships between objects in the scene.

“Using a visual representation only might make it more difficult to reconstruct the image,” Lin continued, “but using a semantic representation like CLIP that incorporates text such as the image’s description, is more coherent with how the brain processes information.”

“The science in this is whether the structure of the models can tell you something about how the brain works,” Singh added. “And that’s what we are hoping to try to find.”

In another experiment, for instance, the researchers found that the fMRI brain signals encoded a lot of redundant information — so much that even after masking more than 80% of the fMRI signal, the resulting 10–20% contained enough data to reconstruct an image within the same category as the original image, even though they didn’t feed any image information into the signal reconstruction pipeline (they were working solely from fMRI data).

“This work represents a true paradigm shift in the accuracy and clarity of image reconstruction methods,” Sprague said. “Previous work focused on extremely simplistic stimuli, because our modeling approaches were much simpler. Now, with these new image reconstruction methods in hand, we can advance our cognitive computational neuroscience experiments toward using naturalistic, realistic stimuli without sacrificing our ability to generate clear conclusions.”

At the moment, the reconstruction of brain data into “true” images continues to be labor intensive and out of reach of ordinary use, not to mention the fact that each model is specific to the person whose brain generated the fMRI data. But it doesn’t stop the researchers from musing on the implications of being able to decode what a person is thinking, right down to the layers of meaning that are hyper specific to each mind.

“What I find exciting about this project is whether it might be possible to preserve the cognitive state of a person, and see how these states so uniquely define them,” Singh said. According to Sprague, these methods would allow neuroscientists to conduct further studies measuring how brains change their representations of stimuli — including in representations of robust, complicated scenes — across task changes.

“This is a critical development that will answer fundamental questions about how brains represent information during dynamic cognitive tasks, including those requiring attention, memory and decision-making,” he said.

One of the areas they are now exploring is finding out what and how much is shared between brains so AI models can be constructed without having to start from zero each time.

“The underlying idea is that the human brain across many subjects share some hidden latent commonalities,” said Christos Zangos, a doctoral student researcher in Singh’s lab. “And based on those, currently I’m working on the exact same framework, but I’m trying to train with a different partition of the data set to see to what extent, using small amounts of data, we could build a model for a new subject.”

Source: UC Santa Barbara


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