Promising stem cell approach to correct photoreceptor cell degeneration causing visual decline, blindness

 A preclinical study using stem cells to produce progenitor photoreceptor cells—light-detecting cells found in the eye—and then transplanting these into experimental models of damaged retinas has resulted in significant vision recovery. This finding, by scientists at Duke-NUS Medical School, the Singapore Eye Research Institute and the Karolinska Institute in Sweden, marks a first step toward potentially restoring vision in eye diseases characterized by photoreceptor loss. The research is published in the journal Molecular Therapy.

"Our laboratory has developed a novel method that enables the production of photoreceptor progenitor cells resembling those in human embryos," said Assistant Professor Tay Hwee Goon, first author of the study from Duke-NUS' Center for Vision Research. "Transplantation of these cells into experimental models has yielded partial restoration of the retinal function."

The degeneration of photoreceptors in the eye is a significant cause of declining vision that can eventually lead to blindness and for which there is currently no effective treatment. Photoreceptor degeneration occurs in a variety of inherited retinal diseases, such as retinitis pigmentosa—a rare eye disease that breaks down cells in the retina over time and eventually causes vision loss—and age-related macular degeneration, a leading cause of vision impairment worldwide.

Tay and her team developed a procedure to grow human embryonic stem cells in the presence of purified laminin proteins that are involved in normal development of human retinas. In the presence of the laminins, stem cells could be directed to differentiate into photoreceptor progenitor cells responsible for converting light into signals that are sent to the brain.

When these cells were transplanted into damaged retinas, the preclinical models showed significant recovery of vision. A diagnostic test called electroretinogram also identified significant recovery in the retinas via electrical activity in the retina in response to a light stimulus. The transplanted cells established connections with surrounding retinal cells and nerves in the inner retina. They also survived and functioned for many weeks after transplantation.

Moving forward, the team hopes to refine their method to make it simpler and achieve more consistent results than earlier attempts to explore stem cell therapy for photoreceptor cell replacement.

"It is exciting to find these results, which suggest a promising route towards using stem cells to treat those forms of visual deterioration and blindness caused by the loss of photoreceptors," said Dr. Helder Andre, Head of Molecular and Cellular Research from Karolinska Institute's Department of Clinical Neuroscience and a senior author of the study.

Associate Professor Enrico Petretto, Director of the Center for Computational Biology at Duke-NUS and the study's bioinformatics analysis lead, added, "Our method may also be useful for understanding the molecular and cellular pathways that drive the progression of macular degeneration, perhaps leading to the development of other therapeutic approaches."

The next challenge for the researchers is to explore the efficacy of their method in models of photoreceptor degeneration that more closely match the human condition.

"If we get promising results in our future studies, we hope to move to clinical trials in patients," said Professor Karl Tryggvason, from Duke-NUS' Cardiovascular and Metabolic Disorders Program, and the corresponding author of the study. "That would be an important step towards for being able to reverse damage of the retina and restore vision."

The protocol underlying the procedure developed by Tay has since been licensed to Swedish biotech start-up Alder Therapeutics.

More information: Hwee Goon Tay et al, Photoreceptor laminin drives differentiation of human pluripotent stem cells to photoreceptor progenitors that partially restore retina function, Molecular Therapy (2023). DOI: 10.1016/j.ymthe.2022.12.012

https://medicalxpress.com/news/2023-04-stem-cell-approach-photoreceptor-degeneration.html

Drug form of traditional Chinese medicine iimproves survival of mice with brain tumors

 A new study shows how a drug made from a natural compound used in traditional Chinese medicine works against malignant brain tumors in mice, creating a promising avenue of research for glioblastoma treatment.

In the study, published in Cell Reports Medicine, researchers showed how a formulation of the compound, called indirubin, improved the survival of mice with malignant brain tumors. They also tested a new formulation that was easier to administer, taking the potential pharmaceutical approach one step closer to clinical trials with human participants.

"The interesting thing about this drug is that it targets a number of important hallmarks of the disease," said Sean Lawler, lead author and a Brown University associate professor of pathology and laboratory medicine. "That's appealing because this type of cancer keeps finding ways around individual mechanisms of attack. So if we use multiple mechanisms of attack at once, perhaps that will be more successful."

The research team included scientists from Brown's Legorreta Cancer Center and School of Engineering; the department of neurosurgery at Brigham and Women's Hospital/Harvard Medical School; and Phosphorex, Inc./Cytodigm, Inc.

Glioblastoma is the most common and aggressive type of brain cancer. The standard of care is chemotherapy, radiation and surgery, which may improve symptoms but don't cure or stop the cancer.

Indirubin is a natural product present in indigo plants and a constituent of the traditional Chinese medicine Dang Gui Long Hui Wan, which has been used in the treatment of chronic myelogenous leukemia, according to the researchers. Derivatives of the indirubin have shown potential for the treatment of cancer through a range of mechanisms.

Research published 10 years ago by Lawler and others showed that indirubin slowed the growth of glioblastoma tumors in mice. However, he said, the researchers weren't able to explain why. What's more, the modified drug wasn't very easy to work with, making it challenging for scientists to test dosage levels or efficiently deliver it to the tumor.

As the scientists continued to research the compound, they were contacted by the Massachusetts-based biomedical company Phosphorex, which develops technology to improve pharmaceutical formulations. Phosphorex had patented a formulation of indirubin, called 6'-bromoindirubin acetoxime (BiA), which made the compound easier to use as an injectable cancer treatment.

The researchers tested the nanoparticle formulation of BiA on glioblastoma tumors in mice, focusing on how the drug would affect the immune system.

Not only did BiA slow the growth and proliferation of tumor cells (confirming the results of previous studies), but it also improved survival via effects on important immunotherapeutic targets.

"The drug impacted the immune system in these mouse experiments in a way that we think could enhance clinical immunotherapy in humans," explained Lawler, whose lab therapeutic approaches for the treatment of brain cancer.

The researchers will continue to test the drug to see how it interacts with chemotherapy and radiation, with the aim of developing clinical trials for participants with glioblastoma. While scientists have been studying glioblastoma for decades, Lawler said that there haven't been many significant therapeutic breakthroughs, until now.

"Over the past 20 years or so, there haven't been many findings of note that have really impacted survival in a meaningful way, so we are very eagerly looking for new approaches," Lawler said. "This research offers a new approach, and that's why we're so excited about it."

More information: Mykola Zdioruk et al, PPRX-1701, a nanoparticle formulation of 6′-bromoindirubin acetoxime, improves delivery and shows efficacy in preclinical GBM models, Cell Reports Medicine (2023). DOI: 10.1016/j.xcrm.2023.101019

https://medicalxpress.com/news/2023-04-drug-traditional-chinese-medicine-compound.html

New UK smart motorway plans being scrapped

 Plans for all new smart motorways have been scrapped, it has been announced.

Fourteen smart motorways will be removed from government road-building plans due to a lack of public confidence and financial pressures, the Department for Transport said.

Smart motorways are a stretch of road where technology is used to regulate traffic flow and ease congestion.

They also use the hard shoulder as an extra lane of traffic, which critics claim has led to road deaths.

Prime Minister Rishi Sunak said "all drivers deserve to have confidence in the roads they use to get around the country".

Existing smart motorways - which make up 10% of England's motorway network - will remain but will be undergo a safety refit so there are more emergency stopping places.

But the 14 planned smart motorways - including 11 that had already been paused and three earmarked for construction - will now not be built.

The government said constructing the schemes would have cost more than £1bn, while cancelling them would allow more time to track public confidence in smart motorways over a longer period.

Mr Sunak, who pledged to ban smart motorways during his leadership campaign last year, said: "Many people across the country rely on driving to get to work, to take their children to school and go about their daily lives and I want them to be able to do so with full confidence that the roads they drive on are safe."

Transport Secretary Mark Harper said: "Today's announcement means no new smart motorways will be built, recognising the lack of public confidence felt by drivers and the cost pressures due to inflation."

Smart motorways were developed in order to create more capacity and cut congestion without having to spend extra money and cause disruption by building whole new roads.

However, they have been criticised by MPs and road safety campaigners, including the AA and RAC.

Claire Mercer, whose husband died on a smart motorway in South Yorkshire in 2019, welcomed the move but pledged to continue campaigning for the hard shoulder to return on every road.

Jason Mercer and another man, Alexandru Murgeanu, died when they were hit by a lorry on the M1 near Sheffield after they stopped on the inside lane of the smart motorway following a minor collision.

Mr Mercer's wife Clare Mercer said: "I'm particularly happy that it's been confirmed that the routes that are in planning, in progress, have also been cancelled. I didn't think they'd do that.

"So it's good news, but obviously it's the existing ones that are killing us. And I'm not settling for more emergency refuge areas."

Mrs Mercer's MP, Labour's Sarah Champion for Rotherham, said she was relieved the government had listened to motorists. But she said she wanted to know if schemes currently in construction would be restored and why a ban had taken so long despite a government review and two parliamentary select committee inquiries.

AA president Edmund King said: "We have had enough coroners passing down their deadly and heart-breaking judgments where the lack of a hard shoulder has contributed to deaths.

"At last the government has listened and we are delighted to see the rollout of smart motorways scrapped… We would also like to see the hard shoulder reinstated on existing stretches in due course."

What is a smart motorway?

There are three main types:

• controlled, which have a permanent hard shoulder, but use technology such as variable speed limits to adjust traffic flows

• dynamic, where the hard shoulder can be opened up at peak times and used as an extra lane; when this happens, the speed limit is reduced to 60mph

• all-lane running, where the hard shoulder has been permanently removed to provide an extra lane; emergency refuge areas are provided at regular intervals for cars that get into trouble

All three models use overhead gantries to direct drivers. Variable speed limits are introduced to control traffic flow when there is congestion, or if there is a hazard ahead. These limits are controlled by speed cameras.

Seven of the 14 schemes that have been cancelled were going to involve converting 'dynamic' smart motorways to 'all-lane running' roads where the hard shoulder is permanently removed - but they will now remain dynamic where the hard shoulder can be opened up to be an extra lane at busy times.

Meanwhile, previously announced plans to safety refit existing smart motorways are being progressed so there will be 150 more emergency stopping places across the network, as well as further improved stopped vehicle detection technology.

Construction of two stretches of smart motorway from junctions six to eight on the M56 and from 21a to 26 on the M6 will continue as they are already more than three quarters complete.

The following schemes have been cancelled:

New all lane running smart motorways

M3 junction 9-14

M40/M42 interchange

M62 junction 20-25

M25 junction 10-16

Dynamic hard shoulder to all lane running conversions

M1 junction 10-13

M4-M5 interchange (M4 junction 19-20 and M5 junction 15-17)

M6 junction 4-5

M6 junction 5-8

M6 junction 8-10a

M42 junction 3a-7

M62 junction 25-30

Pipeline schemes

M1 North Leicestershire

M1 junctions 35A-39 Sheffield to Wakefield

M6 junctions 19- 21A Knutsford to Croft

https://www.bbc.com/news/uk-65288852

Poland, Hungary ban grain and food imports from Ukraine; Kyiv unhappy

 Poland and Hungary have decided to ban imports of grain and other food from neighbouring Ukraine to protect the local agricultural sector, the two governments said on Saturday, after a flood of supply depressed prices across the region.

Ukraine expressed regret about the Polish decision, saying that "resolving various issues by unilateral drastic actions will not accelerate a positive resolution of the situation".

After Russia's invasion blocked some Black Sea ports, large quantities of Ukrainian grain, which is cheaper than that produced in the European Union, ended up staying in Central European states due to logistical bottlenecks, hitting prices and sales for local farmers.

In a letter to the European Commission last month, the prime ministers of five eastern European countries said the scale of the increase in products like grains, oilseeds, eggs, poultry and sugar had been "unprecedented", and said tariffs on Ukrainian agricultural imports should potentially be considered.

The impact of the oversupply has created a political problem for Poland's ruling Law and Justice Party (PiS) in an election year, with the economy mired in stagflation.

"Today, the government has decided on a regulation that prohibits the entry, importation of grain into Poland, but also dozens of other types of food (from Ukraine)," PiS leader Jaroslaw Kaczynski said during a party convention.

The list of these goods, which will range "from grain to honey products, very, very many things", will be included in the government regulation, he added.

Ukraine's ministry of agrarian policy and food said the Polish ban contradicted existing bilateral agreements on exports, and called for talks to settle the issue.

"We understand that Polish farmers are in a difficult situation, but we emphasize that Ukrainian farmers are in the most difficult situation right now," it said in a statement.

Later on Saturday nationalist Hungarian Prime Minister Viktor Orban's government joined the ban, saying the status quo would cause severe damage to local farmers.

Hungary did not give details on when its ban on grain and other food imports would go into effect, but said it will expire at the end of June.

Poland's Kaczynski said: "We are and remain unchanged friends and allies of Ukraine. We will support her and we support her. ... But it is the duty of every state, every authority, good authority in any case, to protect the interests of its citizens."

Kaczynski said Poland was ready to start talks with Ukraine to settle the grain issue.

Hungary's government said it hoped for changes in regulation at the EU level, including a re-thinking of the elimination of import duties on Ukrainian produce.

https://www.marketscreener.com/news/latest/Poland-Hungary-ban-grain-and-food-imports-from-Ukraine-Kyiv-unhappy--43501406/

How AI Can Track, Manipulate Voters

 by Kevin Stocklin via The Epoch Times (emphasis ours),

How well do artificial intelligence (AI) programs know us humans?

In most cases, it’s quite well and, in some ways better than we know ourselves.

A study by AI experts at Brigham Young University, titled “Out of One, Many: Using Language Models to Simulate Human Samples,” found that predictive AI programs exhibited a striking degree of what they call “algorithmic fidelity,” or precise mapping to actual human behavior.

“Because these AI tools are basically trained on stuff that humans produce, things that we write, documents we make, websites we write, they can reflect back to us a lot of interesting and important things about ourselves,” Ethan Busby, political psychologist and co-author of the study, told The Epoch Times. “Kind of like if someone read your diary from start to finish, they would know a lot of things about you, and you’re not going to like every single thing.

“In a similar way,” Busby said, “these tools have read so many things that humans have produced, and they can replicate or say back to us things about ourselves that we didn’t necessarily know.”

The study sought to analyze human behavior in the context of elections and asked how accurately a GPT-3 language model could predict voting patterns based on socio-demographic factors like a person’s gender, age, location, religion, race, and economic status. The authors used these factors to create “silicon samples,” or composite personas based on varying combinations of these attributes.

“You can basically ask these tools to put themselves in a specific frame of mind and pretend to be essentially this person, pretend to have these characteristics,” Busby said. They asked the program how these “silicon samples” would vote in specific campaigns, then they compared the results to actual voters’ behavior in elections between 2012 and 2020, using data from the American National Elections studies.

For example, Busby said, regarding the 2016 election, “We could say what kinds of groups are going to be pivotal in Ohio?” What they found was that AI quickly learned to accurately predict how people would vote, based on their attributes.

Left and Right Decry AI, When It Costs Elections

Artificial intelligence is highly useful to organizations that want to target things like political messaging campaigns or fundraising efforts. But some political analysts have raised red flags about this, inferring unfairness and election interference. Their degree of outrage, however, largely depends on whether their candidates or causes succeeded or failed.

In 2017, The Guardian, a left-wing British newspaper, wrote a series of articles claiming that conservative tech entrepreneur Robert Mercer, whom it called “the big data billionaire waging war on the mainstream media,” had financed a campaign strategy using AI to circumvent mainstream media narratives. This, the paper alleged, illicitly swayed voters in favor of Donald Trump, resulting in his victory in the presidential election in 2016.

https://www.zerohedge.com/political/how-ai-can-track-manipulate-voters

Virginia schools anti-discrimination program might be illegal: courts

 A Northern Virginia school district’s anti-discrimination program may actually violate the First Amendment, an appellate court ruled this week.

The court determined that Loudoun County Public Schools’ “Bias Incident Reporting System” may have a “chilling effect” on the speech of conservative students, who say their views on race and gender are controversial. They ruled that a 2021 lawsuit, filed by three parents only a year after the program was implemented, could now move forward.

“Allegations are sufficient to show that the bias reporting system caused the parents’ children to experience a non-speculative and objectively reasonable chilling effect on their speech,” the court said.

The parents also requested the district to disable an ambassador program which facilitates group conversations between select students and administrators about anonymous bias incidents at schools.

The district argued that the programs are intended to educate and inform students on how to reduce the number of bias incidents in their schools.

“They allege their children’s views plausibly fell within what Student Equity Ambassadors in presentations about the program defined as microaggressions,” the court decision reads. “And the parents allege that their children refrained from speaking on these issues because they feared that, if they did, fellow LCPS students would accuse them of bias.”

The judge said there was no evidence that students were disciplined or substantively harmed by the program, or that the program caused any further “self-censoring” than normal social pressures.

The ruling also states that the ambassador program can not be challenged, but arguments against the bias reporting system will be considered.

A Loudoun County schools spokesperson told The Washington Post that the bias reporting system has never been implemented due to the pending suit.

“(The Ambassador Program is) active and is open to all students who display a passion for equity, are willing to engage in conversations, will listen to learn, and will represent the voice of their peers,” the spokesperson said.

The lawsuit was filed during the peak of debates over the role of discussions of race and gender in schools. Virginia Gov. Glenn Youngkin (R) centered his campaign on the controversy and was elected in 2021, saying that schools should not discuss those topics.

The parents’ case was first dismissed in a lower court last year.

https://thehill.com/regulation/court-battles/3952298-virginia-schools-anti-discrimination-program-might-be-illegal-courts/

Leaked documents include assessment of Taiwan ability to ward of Chinese air attack: WaPo

 Leaked U.S. military documents include Pentagon assessments that Taiwan may be poorly equipped to hold off a Chinese air attack, The Washington Post reports.

The assessments say Chinese air power would likely overwhelm Taiwanese defenses and that Chinese use of civilian ships for military purposes, among other things, makes it difficult for U.S. spy agencies to see an attack coming, according to the Post.

The assessments, obtained by the outlet, are reportedly among the wide array of sensitive and classified military documents recently leaked online. An Air National Guardsman was arrested this week in connection with the leak and charged with violating the Espionage Act.

The leaks come at a time when Chinese-American relations are at a low point, and as the U.S. has underlined its commitment to Taiwan’s defense in the event of a potential Chinese attack.

Last week, House Speaker Rep. Kevin McCarthy (R-Calif.) met with Taiwanese President Tsai Ing-wen in Los Angeles, becoming the highest ranking American to meet with a Taiwanese leader on U.S. soil. Former Speaker Rep. Nancy Pelosi (D-Calif.) visited Taiwan last year.

The Pentagon analysis indicates that the Chinese Air Force would have a strong chance of asserting control in the skies early in a conflict with Taiwan, according to the Post.

The assessments also find Taiwanese military and civilian preparedness inadequate, the outlet reported. They say that the Taiwanese policy to fire two air-defense missiles at each target could be overwhelmed by a “high-volume” Chinese attack, and that civilian air raid siren drills are not effective in preparing for a “real-world event,” per the Post.

But other analysis in the documents predict that a potential Chinese invasion of Taiwan would still be difficult, according to the outlet. One assessment reportedly notes that any amphibious invasion of Taiwan would likely be hampered by difficulties in delivering gasoline, meaning the U.S. and Taiwan could thwart it early on. It further noted that China’s best strategy to enable refueling would be to seize Taipei’s port, something its military has not trained how to do, the Post reported.

China has ramped up military exercises near Taiwan in recent months as a show of force. That includes a ballistic missile barrage near the island following Pelosi’s visit.

The assessments said the increased Chinese military activity around Taiwan makes it more difficult for the intelligence community to accurately gauge a potential escalation, according to the Post.

Pentagon documents also criticize Taiwanese military planning, the outlet reported. They said air defense forces cannot see the location of all units at a given time and do not possess radios to securely communicate, and that plans to expand mandatory conscription next year from four months to a year would not significantly improve defense, according to the Post.

Another assessment reportedly outlines Chinese space warfare capabilities. Documents say that China would be likely to attempt to disable U.S. satellites in the case of an invasion, and that it possesses a range of weaponry that could be used to “deter, disrupt, and, if necessary, defeat” U.S. attempts to defend Taiwan, according to the Post.

https://thehill.com/policy/defense/3952204-leaked-documents-include-troubling-assessment-of-taiwans-ability-to-ward-of-chinese-air-attack-report/