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DNA from ancient population in Southern China suggests Native Americans’ East Asian roots

The lateral view of the skull unearthed from Red Dear Cave. Credit: Xueping Ji

For the first time, researchers successfully sequenced the genome of ancient human fossils from the Late Pleistocene in southern China. The data, published July 14 in the journal Current Biology, suggests that the mysterious hominin belonged to an extinct maternal branch of modern humans that might have contributed to the origin of Native Americans.

“Ancient DNA technique is a really powerful tool,” Su says. “It tells us quite definitively that the Red Deer Cave people were modern humans instead of an archaic species, such as Neanderthals or Denisovans, despite their unusual morphological features,” he says.

The researchers compared the genome of these fossils to that of people from around the world. They found that the bones belonged to an individual that was linked deeply to the East Asian ancestry of Native Americans. Combined with previous research data, this finding led the team to propose that some of the southern East Asia people had traveled north along the coastline of present-day eastern China through Japan and reached Siberia tens of thousands of years ago. They then crossed the Bering Strait between the continents of Asia and North America and became the first people to arrive in the New World.

The journey to making this discovery started over three decades ago, when a group of archaeologists in China discovered a large set of bones in the Maludong, or Red Deer Cave, in southern China’s Yunnan Province. Carbon dating showed that the fossils were from the Late Pleistocene about 14,000 years ago, a period of time when modern humans had migrated to many parts of the world.

The reproduced portrait of the Red Deer Cave People or Mengziren. Credit: Xueping Ji

From the cave, researchers recovered a hominin skull cap with characteristics of both modern humans and archaic humans. For example, the shape of the skull resembled that of Neanderthals, and its brain appeared to be smaller than that of modern humans. As a result, some anthropologists had thought the skull probably belonged to an unknown archaic human species that lived until fairly recently or to a hybrid population of archaic and modern humans.

In 2018, in collaboration with Xueping Ji, an archaeologist at Yunnan Institute of Cultural Relics and Archaeology, Bing Su at Kunming Institute of Zoology, Chinese Academy of Sciences, and his colleagues successfully extracted ancient DNA from the skull. Genomic sequencing shows that the hominin belonged to an extinct maternal lineage of a group of modern humans whose surviving decedents are now found in East Asia, the Indo-China peninsula, and Southeast Asia islands.

The finding also shows that during the Late Pleistocene, hominins living in southern East Asia had rich genetic and morphologic diversity, the degree of which is greater than that in northern East Asia during the same period. It suggests that early humans who first arrived in eastern Asia had initially settled in the south before some of them moved to the north, Su says.

The excavation site of Maludong (Red Deer Cave). Credit: Xueping Ji

“It’s an important piece of evidence for understanding early human migration,” he says.

Next, the team plans to sequence more ancient human DNA by using fossils from southern East Asia, especially ones that predated the Red Deer Cave people.

“Such data will not only help us paint a more complete picture of how our ancestors migrate but also contain important information about how humans change their physical appearance by adapting to local environments over time, such as the variations in skin color in response to changes in sunlight exposure,” Su says.







Middle Pleistocene human skull reveals variation and continuity in early Asian humans


More information:
Bing Su, A Late Pleistocene human genome from Southwest China, Current Biology (2022). DOI: 10.1016/j.cub.2022.06.016. www.cell.com/current-biology/f … 0960-9822(22)00928-9

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Brain size vs. body size and the roots of intelligence

Behavior that we’d consider intelligent is oddly widespread in the animal kingdom. Animals with very different brains from ours—a species of octopus and various birds—engage with tools, to give just one example. It seems intuitive that a brain needs a certain level of size and sophistication to enable intelligence. But figuring out why some species seem to have intelligence while closely related ones don’t has proven difficult—so difficult that we don’t really understand it.

One of the simplest ideas has been that size is everything: have a big enough brain, and you at least have the potential to be smart. But lots of birds seem to be quite intelligent despite small brains—possibly because they cram more neurons into a given volume than other species. Some researchers favor the idea that intelligence comes out of having a large brain relative to your body size, but the evidence there is a bit mixed.

This week, a team of researchers published a paper arguing that the answer is a little of both: relative and absolute size matter when it comes to the brain. And they argue that a specific approach to brain development helps enable it.

What makes smarts?

To study what makes for intelligence, you need to define the word. And that can be a slippery thing to nail down. We all know (and/or are) people who are brilliant in some circumstances yet idiotic in others. Similarly, an animal might engage in tool use but be unable to figure out how to find its way around a simple barrier. So defining intelligence in different ways may produce different answers to whether a given species qualifies.

For the current work, the focus was on the mental facilities of birds. The researchers defined intelligence as innovation or the tendency to demonstrate novel behaviors. (Owls had to be excluded from the study because their behaviors are difficult to observe.) The number of papers reporting innovative behaviors was normalized by dividing it by the total number of papers describing any behavior in the species to adjust for the fact that some are simply better studied than others.

The researchers then compared that to brain features with three questions in mind. One was whether intelligence correlated with specific brain regions—specifically an area called the pallium in birds, which appears to handle many of the same functions as the neocortex in humans. This area is, among other things, where the brain integrates sensory information and plans activities.

Taking advantage of a system that allows them to count the number of neurons present in different areas of the brain, the researchers could test whether intelligence correlated with the size of the brain as a whole, with the pallium in specific, or with the ratio of brain size to body size. The research team could also look at the developmental history of the brain in intelligent species and try to understand how any correlations they discovered came about.

¿Por qué no los dos?

In general, bigger brains meant more complicated behavior. “The number of neurons in the entire brain is positively associated with behavioral innovation propensity,” the authors conclude, “particularly technical innovations that are assumed to require more advanced cognition.” But controlling for body size showed that the relative size of the brain still mattered. If a species had more neurons than you’d expect based on their body size, then they were more likely to engage in complex behaviors.

The researchers suggest that we’ve tended to view this as an either/or situation—it’s got to be either total brain size or the brain-to-body ratio. By setting up our analyses to compare the two, we’ve limited our ability to identify that both correlations seem true simultaneously. When specific brain regions were analyzed independently, the pallium was the most significant region associated with complicated bird behavior; the cerebellum also contributed, but to a smaller extent.

Consistent with the overall conclusions, the number of neurons in the pallium went up with both absolute brain size and brain size relative to body size. Neurons in the cerebellum went up largely as a function of absolute brain size. And there was no clear pattern in the number of neurons in the brainstem.

Corvids and parrots are noted as having some of the most complex behaviors in the bird world. Analyzing them separately, the researchers show that the number of neurons scales rapidly with body size—far more quickly than other groups of birds. How do these species end up with an unusually large number of neurons? They tend to have a longer developmental period after they hatch, and this time is used to pack more neurons into the pallium. Parrots tend to continue generating neurons for longer, and the neurons don’t mature as quickly as others.

Obviously, we’ll want to do a similar analysis with groups other than birds to find out whether this is a general rule or how birds have produced species with varied intelligence. But, even if this finding is a general indication of “how,” it really doesn’t help us answer “why?” The researchers suggest that parrots tend to be larger, long-lived birds. So, the payoff time for having sophisticated mental hardware is longer, even if developing said hardware takes longer.

Which seems pretty intuitive until you start thinking about the exceptions. Corvids like crows and jays only have a life span of about seven years, yet are still capable of some very sophisticated behavior. Jays aren’t even especially large birds. And plenty of large, long-lived birds haven’t ended up with any behaviors indicating intelligence. So, even if this does hold up, there’s a lot we don’t know about why some animals end up intelligent.

Nature Ecology and Evolution, 2022. DOI: 10.1038/s41559-022-01815-x  (About DOIs).

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Indian roots, many career pivots, Apple Health VP Dr Sumbul Desai knows everything finally adds up

If the rebel within her had prevailed, Dr Sumbul Desai would have been a journalist or a media honcho. But after many pivots in her career, the Sweden-born with Indian roots is now one of the most influential women in global tech — as Apple’s VP-Health.

“You’d never think that all of those stops you are going to make are going to help you with your ultimate role. All that learning ends up putting you exactly where you should be,” Desai told The Indian Express on video call from California.

Desai joined Apple five years ago to strengthen the Cupertino-based tech giant’s foray into personal health technologies. Before that, she was Vice Chair of Strategy and Innovation in the Department of Medicine at Stanford Medicine as well as Associate Chief Medical Officer at Stanford Healthcare.

And yet, those early stints with the Walt Disney Company and ABC News still stand out in her impressive resume. “My parents wanted me to be either a doctor or an engineer,” says Desai. Echoing millions of Indians across the world, her parents, who moved from India to Sweden and then the US, were no different when it came to their children, she points out.

“(But) I always wanted to do something more than that and so when I started my undergraduate career, I was initially hoping to go to a bachelor’s program in liberal arts. I’d also gotten into a six-year Bachelors of Science in MD program, which is very rare,” she says. “I did not want to go and, when I was going through the application process, gave smart-alec answers hoping the admission officers wouldn’t take me seriously.” That strategy didn’t go as planned. “That probably made me sound well rounded…I got in.”

AppleÕs vice president of health Sumbul Ahmad Desai talks about new Health features coming to iPhone and Apple Watch, as seen in this still image from the keynote kicking off WWDC22. (Photo by Apple Inc.)

But though she joined Rensselaer Polytechnic Institute, a reputed technological research university in New York, mostly because her father was really keen, she did not do particularly well in the first semester. “I was not trying very hard.” That’s when her father gave in and told her to do what she wanted. “I changed my major to Computer Science with a minor in Communications.”

That’s how Desai’s career started with the media industry where she transitioned to the business side and worked on strategy. Then came another twist when, in August 2001, she was visiting her family in New York and her mother suffered a stroke. “She went immediately into a coma and was critically ill in the ICU on a ventilator. For me, that day, life fundamentally changed,” says Desai.

A month later, when ICUs in the city had to be cleared to make way for 9/11 survivors, she had to take care of her mother in a rehab facility. “One of the pieces of advice that one of the physicians had given me on the way out was you have to empower and really advocate for your mother because she can’t,” says Desai, adding that her mother was in hospital for a year and had to relearn everything from walking to breathing.

“That changed my perspective on healthcare to see that when it comes together in a really beautiful way, it can really be a multi-faceted journey. It also is very much a collaboration across many disciplines… The outcome can either be really good or the collaboration doesn’t work. That was the driving force why I decided to go back to medical school later in life,” she says.

Medicine also revived her link with India after she had interned at Doordarshan and Times of India for her minor. “At Escorts (Now Fortis Escorts) in Delhi, I spent the day with some cardiologists, then at Holy Family, and also with a nephrologist who had a private practice.” The complexity of cases she saw in the hospitals of Delhi “solidified” her desire to go into healthcare “because part of why I wanted to (do that) was how do you give back to people and how you have an impact”.

Desai is aware that though she was born in Sweden and spent most of her life in the US, the connection with India is a big part of who she is. “My mother is from Delhi and my father grew up in UP, near Meerut. We come from a family of very proud Indians. We used to go back to India almost every other year growing up. When I was younger, it was almost every summer and then as we became a little older, it became every other year.”

Desai says those visits to be with her grandparents also made her more grounded. “Whenever you go back, you really go back to your roots and it grounds you, you always come back a little bit more grounded. There’s something about the culture, the people… that’s something that I like really long for and I miss,” she says.

She is quick to add though that this could also be a romanticised view of reality since “obviously, the world is changing there, too”.

Although she had rebelled against her parents’ wish to see her as a doctor or engineer, Desai now appreciates what they were trying to achieve. “The one thing that I’m blessed with is that as a woman, and especially as a Muslim woman, my parents always felt that I should be independent and be able to support myself. It was never like you have to go off and get married…it was very much you need to have a career and support yourself and find a stable way of doing that. And to them, that was engineering and medicine.”

As for her current role in Apple, Desai says her experience in communication helps. “The ability to communicate is really critical, because you want to be able to take very complex topics and figure out how to distill it down in a simple way so that it’s understandable,” she says.

The Apple Health team spends “a lot of time obsessing about how we simplify the message that the individual gets so they really understand in the moment what we are telling them”. She says that is where the ability to take complex messages and simplify it as a physician is “incredibly valuable”. “I think all of my experiences amounted to being able to drive our teams to do that in a meaningful way.”

As someone who has been working on tech that alerts millions of people on their health status based on data their body generates, Desai says it’s an “honour” that people choose to use these devices every day. She says it is about empowering individuals to feel they are in control of their health. “…privacy is central and the core to everything we do so that the individual owns the data on their device, and is in control of that data. That’s also part of the empowerment,” she says.

Desai is clear Apple does not want to provide information for information’s sake, “because that doesn’t do anything”. “We want the individual to not just have an understanding of the scientific backing of these actual insights, but also the medical community because we really believe that partnership is really sacred and we want to enrich that partnership so that you have more information so the practitioner can rely on it from a scientific basis, has more information to understand what’s going on with an individual,” she says.

Desai teaches “at times” in Stanford and has helped with Covid-19 work. But those “little data moments” in Apple continue to fascinate because they are “almost like snapshots and pictures like you take pictures of your everyday life with the camera”.

“Along with the traditional clinical metrics, it just gives us more of a comprehensive data set to be able to potentially make clinical decisions. Our devices are never meant for diagnosis. What they are meant for is additional screening, or additional information so that you can make more actionable decisions,” she says.

Despite the huge advancements in health tech in recent years, especially because of the pandemic, Desai says there’s a lot more to be done. “As advanced as technology is, when it comes to technology and healthcare, we are still very early in our journey…But I do think an individual now feels more empowered about asking the right questions.”



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3-D Printing Grows Beyond Its Novelty Roots

DEVENS, Mass. — The machines stand 20 feet high, weigh 60,000 pounds and represent the technological frontier of 3-D printing.

Each machine deploys 150 laser beams, projected from a gantry and moving quickly back and forth, making high-tech parts for corporate customers in fields including aerospace, semiconductors, defense and medical implants.

The parts of titanium and other materials are created layer by layer, each about as thin as a human hair, up to 20,000 layers, depending on a part’s design. The machines are hermetically sealed. Inside, the atmosphere is mainly argon, the least reactive of gases, reducing the chance of impurities that cause defects in a part.

The 3-D-printing foundry in Devens, Mass., about 40 miles northwest of Boston, is owned by VulcanForms, a start-up that came out of the Massachusetts Institute of Technology. It has raised $355 million in venture funding. And its work force has jumped sixfold in the past year to 360, with recruits from major manufacturers like General Electric and Pratt & Whitney and tech companies including Google and Autodesk.

“We have proven the technology works,” said John Hart, a co-founder of VulcanForms and a professor of mechanical engineering at M.I.T. “What we have to show now is strong financials as a company and that we can manage growth.”

For 3-D printing, whose origins stretch back to the 1980s, the technology, economic and investment trends may finally be falling into place for the industry’s commercial breakout, according to manufacturing experts, business executives and investors.

They say 3-D printing, also called additive manufacturing, is no longer a novelty technology for a few consumer and industrial products, or for making prototype design concepts.

“It is now a technology that is beginning to deliver industrial-grade product quality and printing in volume,” said Jörg Bromberger, a manufacturing expert at McKinsey & Company. He is the lead author of a recent report by the consulting firm titled, “The Mainstreaming of Additive Manufacturing.”

3-D printing refers to making something from the ground up, one layer at a time. Computer-guided laser beams melt powders of metal, plastic or composite material to create the layers. In traditional “subtractive” manufacturing, a block of metal, for example, is cast and then a part is carved down into shape with machine tools.

In recent years, some companies have used additive technology to make specialized parts. General Electric relies on 3-D printing to make fuel nozzles for jet engines, Stryker makes spinal implants and Adidas prints latticed soles for high-end running shoes. Dental implants and teeth-straightening devices are 3-D printed. During the Covid-19 pandemic, 3-D printers produced emergency supplies of face shields and ventilator parts.

Today, experts say, the potential is far broader than a relative handful of niche products. The 3-D printing market is expected to triple to nearly $45 billion worldwide by 2026, according to a report by Hubs, a marketplace for manufacturing services.

The Biden administration is looking to 3-D printing to help lead a resurgence of American manufacturing. Additive technology will be one of “the foundations of modern manufacturing in the 21st century,” along with robotics and artificial intelligence, said Elisabeth Reynolds, special assistant to the president for manufacturing and economic development.

In May, President Biden traveled to Cincinnati to announce Additive Manufacturing Forward, an initiative coordinated by the White House in collaboration with major manufacturers. The five initial corporate members — GE Aviation, Honeywell, Siemens Energy, Raytheon and Lockheed Martin — are increasing their use of additive manufacturing and pledged to help their small and medium-size American suppliers adopt the technology.

The voluntary commitments are intended to accelerate investment and build a broader domestic base of additive manufacturing skills. Because 3-D printing is a high-tech digital manufacturing process, administration officials say, it plays to America’s strength in software. Additive manufacturing, they add, will make American manufacturing less dependent on casting and metalworking done overseas, especially in China.

Additive manufacturing also promises an environmental bonus. It is far less wasteful than the casting, forging and cutting of traditional manufacturing. For some metal parts, 3-D printing can cut materials costs by 90 percent and reduce energy use by 50 percent.

Industrial 3-D printing, experts say, has the potential to substantially cut the total expense of making specialized parts, if the technology can be made fast and efficient enough for higher-volume production.

VulcanForms was founded in 2015 by Dr. Hart and one of his graduate students, Martin Feldmann. They pursued a fresh approach for 3-D printing that uses an array of many more laser beams than existing systems. It would require innovations in laser optics, sensors and software to choreograph the intricate dance of laser beams.

By 2017, they had made enough progress to think they could build a machine, but would need money to do it. The pair, joined by Anupam Ghildyal, a serial start-up veteran who had become part of the VulcanForms team, went to Silicon Valley. They secured a seed round of $2 million from Eclipse Ventures.

The VulcanForms technology, recalled Greg Reichow, a partner at Eclipse, was trying to address the three shortcomings of 3-D printing: too slow, too expensive and too ridden with defects.

The start-up struggled to build a first machine that proved its concept workable. But it eventually succeeded. And later versions grew larger, more powerful and more precise.

Its printers, VulcanForms said, now generate 100 times the laser energy of most 3-D printers, and can produce parts many times faster. That print technology is the company’s core intellectual asset, protected by dozens of patents.

But VulcanForms has decided not to sell its machines. Its strategy is to be a supplier to customers in need of custom-made parts.

That approach allows VulcanForms to control the entire manufacturing process. But it is also a concession to the reality that the ecosystem of additive manufacturing is lacking. The company is building each stage of the manufacturing process itself, making its own printers, designing parts, doing final machining and testing.

“We absolutely have to do it ourselves — build the full stack of digital manufacturing — if we are to succeed,” said Mr. Feldmann, who is the chief executive. “The factory is the product.”

The Devens facility has six of the giant printers. By next year, there should be 20, the company said. VulcanForms has scouted four locations for a second factory. In five years, the company hopes to have several 3-D printing factories up and running.

The do-it-yourself strategy also magnifies the risk and the cost for the start-up. But the company has convinced a roster of high-profile recruits that the risk is worth it.

Brent Brunell joined VulcanForms last year from General Electric, where he was an additive manufacturing expert. The concept of using large arrays of lasers in 3-D printing is not new, Mr. Brunell said, but no one had really pulled it off before. After he joined VulcanForms and examined its technology, he said, “it was obvious these guys were onto the next architecture, and they had a process that was working.”

Beside each machine in VulcanForms’s facility, an operator monitors its performance with a stream of sensor data and a camera image of the laser beams at work, piped to a computer screen. The sound of the factory is a low, electronic hum, much like a data center.

The factory itself can be a potent recruiting tool. “I bring them here and show them the machinery,” said Kip Wyman, a former senior manufacturing manager at Pratt & Whitney, who is head of operations at VulcanForms. “The usual reaction is, ‘Heck, I want to be part of that.’”

For some industrial parts, 3-D printing alone is not enough. Final heat treatment and metal machining are needed. Recognizing that, VulcanForms acquired Arwood Machine this year.

Arwood is a modern machine shop that mostly does work for the Pentagon, making parts for fighter jets, underwater drones and missiles. Under VulcanForms, the plan over the next few years is for Arwood to triple its investment and work force, currently 90 people.

VulcanForms, a private company, does not disclose its revenue. But it said sales were climbing rapidly, while orders were rising tenfold quarter by quarter.

Sustained growth for VulcanForms is going to depend on increasing sales to customers like Cerebras, which makes specialized semiconductor systems for artificial intelligence applications. Cerebras sought out VulcanForms last year for help making a complex part for water-cooling its powerful computer processors.

The semiconductor company sent VulcanForms a computer-design drawing of the concept, an intricate web of tiny titanium tubes. Within 48 hours VulcanForms had come back with a part, recalled Andrew Feldman, chief executive of Cerebras. Engineers for both companies worked on further refinements, and the cooling system is now in use.

Accelerating the pace of experimentation and innovation is one promise of additive manufacturing. But modern 3-D printing, Mr. Feldman said, also allows engineers to make new, complex designs that improve performance. “We couldn’t have made that water-cooling part any other way,” Mr. Feldman said.

“Additive manufacturing lets us rethink how we build things,” he said. “That’s where we are now, and that’s a big change.”

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Finding the Biological Roots for the Pathological Social Withdrawal Known as ‘Hikikomori’

Summary: Hikikomori is a mental health disorder identified as a pathological social withdrawal. Researchers have discovered a number of biomarkers in the blood associated with hikikomori.

Source: Kyushu University

Researchers at Kyushu University have identified a number of key blood biomarkers for pathological social withdrawal, known as hikikomori.

Based on their findings, the team was able to distinguish between healthy individuals and hikikomori patients as well as determine the severity of the condition.

According to Japan’s Ministry of Health, Labour, and Welfare, hikikomori is a condition in which individuals do not leave their dwelling and isolate themselves away from society and family for a period exceeding six months.

Also identified as “pathological social withdrawal,” hikikomori is estimated to afflict more than one million people in Japan today.

While it has been historically identified as a Japanese culture-bound syndrome, evidence over the last few decades has shown that it is becoming a global phenomenon, with some fearing the COVID-19 pandemic catalyzing a global wave of hikikomori patients.

In 2013, the Kyushu University Hospital established the world’s first outpatient clinic for hikikomori research in hopes of developing support systems for patients through biological, psychological, and social understanding of the condition.

In a report published in Dialogues in Clinical Neuroscience, lead researcher Takahiro A. Kato of Kyushu University’s Faculty of Medical Sciences explains that while the sociological underpinnings of the condition are carefully studied, major gaps remain in the understanding of the biological aspects of hikikomori.

“Mental illnesses such as depression, schizophrenia, and social anxiety disorder are occasionally observed in hikikomori individuals. However, our past research shows that it is not that simple, and that it is a complex condition with overlaps of different psychiatric and non-psychiatric elements,” explains Kato.

“Understanding what happens biologically will help us greatly in identifying and treating hikikomori.”

The team conducted blood biochemical tests and collected data on the plasma metabolome—small molecules found in blood such as sugars, amino acids, and proteins—from 42 unmedicated hikikomori individuals and compared it with data from 41 healthy volunteers. In total, data for 127 molecules were analyzed.

“Some of our key findings showed that, in the blood of men with hikikomori, ornithine levels and serum arginase activity were higher while bilirubin and arginine levels were lower,” states first author of the paper Daiki Setoyama.

“In both men and women patients, long-chain acylcarnitine levels were higher. Moreover, when this data was further analyzed and categorized, we were able to distinguish between healthy and hikikomori individuals, and even predict its severity.”

Ornithine is an amino acid produced from the amino acid arginine with the help of the enzyme arginase. These molecules are vital in many bodily functions, including blood pressure regulation and the urea cycle.

Bilirubin is made when the liver breaks down red blood cells and is often used as a marker for proper liver function. Patients with major depression and seasonal affective disorder have been reported to have lower blood bilirubin levels.

While it has been historically identified as a Japanese culture-bound syndrome, evidence over the last few decades has shown that it is becoming a global phenomenon, with some fearing the COVID-19 pandemic catalyzing a global wave of hikikomori patients. Image is in the public domain

Finally, acylcarnitines play an important role in supplying energy to the brain. Its levels decrease when patients with depression take selective serotonin reuptake inhibitors.

However, patients with hikikomori differ from patients with depression in that only the long-chain acylcarnitines are elevated in hikikomori whereas short-chain acylcarnitines remain the same.

Says Kato, “Identifying the biomarkers of hikikomori is the first step in uncovering the biological roots of the condition and connecting them to its severity. We hope these findings will lead to better specialized treatments and support for hikikomori.”

See also

“Many questions remain, including understanding the root causes behind these biomarkers. Today, hikikomori is spreading worldwide, thus, we must conduct international investigations to understand the similarities and differences between patients with hikikomori globally,” he concludes.

About this psychology research news

Author: Press Office
Source: Kyushu University
Contact: Press Office – Kyushu University
Image: The image is in the public domain

Original Research: Open access.
“Blood metabolic signatures of hikikomori, pathological social withdrawal” by Daiki Setoyama et al. Dialogues in Clinical Neuroscience


Abstract

Blood metabolic signatures of hikikomori, pathological social withdrawal

Background

A severe form of pathological social withdrawal, ‘hikikomori,’ has been acknowledged in Japan, spreading worldwide, and becoming a global health issue. The pathophysiology of hikikomori has not been clarified, and its biological traits remain unexplored.

Methods

Drug-free patients with hikikomori (n = 42) and healthy controls (n = 41) were recruited. Psychological assessments for the severity of hikikomori and depression were conducted. Blood biochemical tests and plasma metabolome analysis were performed. Based on the integrated information, machine-learning models were created to discriminate cases of hikikomori from healthy controls, predict hikikomori severity, stratify the cases, and identify metabolic signatures that contribute to each model.

Results

Long-chain acylcarnitine levels were remarkably higher in patients with hikikomori; bilirubin, arginine, ornithine, and serum arginase were significantly different in male patients with hikikomori. The discriminative random forest model was highly performant, exhibiting an area under the ROC curve of 0.854 (confidential interval = 0.648–1.000). To predict hikikomori severity, a partial least squares PLS-regression model was successfully created with high linearity and practical accuracy. In addition, blood serum uric acid and plasma cholesterol esters contributed to the stratification of cases.

Conclusions

These findings reveal the blood metabolic signatures of hikikomori, which are key to elucidating the pathophysiology of hikikomori and also useful as an index for monitoring the treatment course for rehabilitation.

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Cardi B Returns To Her Stripper Roots On Cabo Baecation With Offset

The couple packed on the PDA after Cardi showed out on the pole.

Cabo is heating up this Memorial Day long weekend thanks to Offset and Cardi B, who are currently on a baecation in the luxurious Mexican paradise. Their trip kicked off with a flirty photo dump from the mother of two, who flexed her “body in Miu Miu” with her “kitty on meow meow” in a colourful two-piece crochet set while riding on a private jet, and things have only gotten more eventful since then.

Upon arriving to their accommodations, the “Clout” collaborators were met with a beautiful view, although it wasn’t long before tragedy struck as a yacht began to sink right in front of them. Luckily, the boat was empty, but the “Money” rapper still provided devastated commentary as the “big boat” said “Buh-bye!”

Jon Kopaloff/Getty Images

On Sunday, May 29th, it looks like Cardi and her husband hit the town and found themselves in a strip club, where the Hustlers actress didn’t hesitate to hop on the pole and showcase the moves that helped her make money before her rise to fame in the music industry.

“We in Cabo… Where the hoes at?” she tweeted last night. “What’s the vibes for the night?!” Clearly, the vibes for the night were getting hot and heavy with Offset, as that’s exactly what they did, packing on the PDA when the 29-year-old had finished her performance to The Weeknd’s “Earned It.” 

In other news, just a few days before they headed out on vacation, the Migos member made headlines after declaring that Cardi B is his “favourite meal” for a TikTok – read more about that here, and tap back in with HNHH later for more hip-hop news updates.



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Gran Turismo 7 preview: A return to expansive, grindy, car-collecting roots

Sony

If Sony and Polyphony Digital stick to their current deadline, the newest installment of the 25-year-old Gran Turismo franchise should launch on March 4. Gran Turismo 7 will be the first GT game for the PS5 console (there’s a PS4 port for those of us who can’t get a hold of the latest-gen hardware). The game will have a bunch of new features and see the return of plenty of older ones.

Earlier today, Sony published a half-hour “state of play” video showing off GT7, and earlier this week, the company briefed Ars on the new game. Read on to find out what we know—and crucially, what we’re still waiting to find out ahead of the game’s launch,

Gran Turismo 7.”>
Enlarge / This is the world map for Gran Turismo 7.

Sony

When Gran Turismo: Sport debuted in 2017, it left many die-hard GT fans wanting. It solved some long-running issues with the franchise, notably in how it simulated tires. But Sport was almost entirely focused on e-sports and online multiplayer gameplay. To some fans raised on previous games that were giant sandboxes full of cars, this felt like a betrayal.

If I’m describing you, take heart, because GT7 looks like a return to the expansive (if at times grindy) GT universe you probably fell in love with in the late ’90s.

But GT7 is not just for graybeards. The game’s lead designer and Polyphony Digital head honcho Kazunori Yamauchi says that society has changed a lot since 1997. Young people don’t have the same interest in cars as they once had, and GT7 understands that societal shift. Instead, its goal is “exciting people to the allure of cars.”

Enlarge / Did you miss the license tests?Because they’re back.

Sony

Think of GT7 as the car life simulator, Yamauchi says—a sandbox of life with cars, with no clear ending and plenty of mileage for gamers. As ever, you start the game with a small amount of credits and compete in races to earn more, winning prize cars along the way.

To begin with, GT7 will ship with 400 cars, which you’ll find split between Brand Central (for new cars from 2001 through today), Used Cars (which is self-explanatory), and the Legendary Car dealer (where you’ll find notable vehicles that won’t be cheap). And yes, the car wash and oil change are both back where they belong.

The return of customization and tuning will no doubt be welcomed by many. There are hundreds of custom parts you can add to a car; some add performance, while others are more cosmetic, like new wing endplanes or different-colored brake calipers. Each car has an expansive tuning menu, and a “measure” function simulates the effect of your tweaks in real time—something Yamauchi likens to a mini-game.

What won’t be easy is sharing your setups with other players. Despite an always-online requirement—necessary to prevent people from cheating with their saved games, Yamauchi says—the only way to share a setup is to take a screenshot and share that image. (We were told the reason is that players could have different parts installed on the car, and facilitating sharing was too complicated.)

There will also be 34 different race track locations with a total of 90 different raceable layouts—you’ll find all of these in World Circuits. Despite the name, this is a mix of real and fictional tracks, including the return of the much-loved Trial Mountain, among others. Each track also has its own tutorial program, much like in GT: Sport.

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Deep roots of Australia’s geology revealed

Credit: Pixabay

A new study has shown for the first time how Australia’s rich geological history is reflected deep below the Earth’s surface.

Author of the study, Dr. Caroline Eakin from The Australian National University (ANU), said the Australian land mass is made up of different building blocks that fused together over 1.3 billion years ago.

“Australia is an old, stable continent,” Dr. Eakin said.

“Australia’s different building blocks are reflected on the Earth’s surface, but it’s been unclear to what depth these geological differences would be reflected below the Earth’s crust.”

Dr. Eakin used observations of scattered surface waves—known as Quasi-Love waves—created by distant earthquakes to study Australia’s geological makeup.

“These Quasi-Love waves show boundaries deep within and surrounding the Australian continent that correspond to the same tectonic boundaries seen at the surface,” Dr. Eakin said.

“This suggests these kinds of geological features are preserved for billions of years.”

According to Dr. Eakin this new information about what’s happening 100–200 kilometers below the Earth’s surface indicates the deeper part of our continent is just as geologically diverse as the crust.

It is the most detailed analysis of this kind of data in Australia to date, taking into account over 2000 earthquake recordings made at seismometers across the Australian continent.

The study has been published in Communications Earth & Environment.


New study unravels secret to subduction


More information:
Caroline M. Eakin, Quasi-Love wave scattering reveals tectonic history of Australia and its margins reflected by mantle anisotropy, Communications Earth & Environment (2021). DOI: 10.1038/s43247-021-00276-7
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Australian National University

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Deep roots of Australia’s geology revealed (2021, October 8)
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Resident Evil reboot trailer looks like a welcome return to gaming roots

When the first Resident Evil game debuted in 1998, it was an immediate commercial and critical success, spawning several sequel games, comics, novels, and a very lucrative film franchise directed by Paul W.S. Anderson and starring Milla Jovovich. But those films were only loosely based on the games, keeping a few primary characters and the basic concept, but little else. Sony Pictures just dropped the official trailer for its upcoming reboot, Resident Evil: Welcome to Raccoon City, and it looks like it will hew much more closely to the source material than its big-screen predecessors.

(Some spoilers for the first two games in the franchise below, but no major reveals.)

The sixth and final film in the Anderson series was released fairly recently, in 2016. But the franchise made a ton of money, so naturally a complete reboot was in the works by early 2017, with Johannes Roberts (47 Meters Down) at the helm.

Although he was a fan of the preceding franchise, Roberts told IGN earlier this year that he wanted to bring a very different tone to his film. He wanted to stay closer to the Resident Evil and Resident Evil 2 games—even employing the same fixed angles of Spencer Mansion in the first game. “What I loved about the games was that they were just scary, and that’s a lot of what I wanted, that atmosphere. It’s raining constantly, it’s dark, it’s scary, Raccoon City is a rotten character,” he said. “I wanted to… mix it with the fun side, especially with the narrative style of the first game.”

The first Resident Evil game is set in July 1998, as the the fictional Midwestern town of Raccoon City is reeling from a series of brutal murders. The STARS team sends in a Beta unit but soon loses contact with them, then sends its Alpha team to investigate. Attacked by zombie dogs, they take refuge in the abandoned Spencer Mansion—except it’s not really abandoned. All manner of zombies and mutant monsters—the result of bizarre experiments conducted by the Umbrella Corporation using a biological agent called the T-Virus—roam the mansion and its environs.

Players can choose to play STARS agents Chris Redfield or Jill Valentine, and they must find documents containing helpful clues and solve various puzzles to figure out what happened. And of course, there is much fighting against the monsters, including a giant humanoid supersoldier dubbed the Tyrant.

Resident Evil 2 takes place in September 1998, two months after the events of its predecessor. Here, the main characters are Claire Redfield (Chris’ sister) and rookie Police Officer Leon S. Kennedy, who must get out of the city, which has been overrun with zombies. They must battle the Tyrant, who is hunting for yet another mutating biological agent called the G-Virus. (Will these mad scientists at Umbrella Corporation ever learn?) They must also race to create a vaccine for the G-Virus, which can stop the process of mutation in the human body.

Do you remember the 30th night of September?

The trailer for Resident Evil: Welcome to Raccoon City opens with the welcome sign for Raccoon City and the date: September 30, 1998. That places us squarely in the timeframe of Resident Evil 2. True to his word, Roberts seems to have brought not just the look and feel of the game to his film but also most of the characters and several plot points. The cast includes Claire and Chris Redfield (Kaya Scodelario and Robbie Amell, respectively), Jill Valentine (Hannah John-Kamen), and Leon Kennedy (Avan Jogia), who team up to find out the truth about the Umbrella Corporation and Spencer Mansion—and of course, fight off the mutant monsters and hopefully save the world.

William Birkin (Neal McDonough), the mad scientist who conducts the disastrous experiments for the Umbrella Corporation, will clearly play a significant role (as he does in Resident Evil 2). Donal Logue plays corrupt Raccoon City Police Chief Brian Irons, Lily Guy plays the mysterious spy Ada Wong, Tom Hopper and Chad Rook play STARS team members Albert Wesker and Richard Aiken, and Marina Mazepa plays Lisa Trevor, the unfortunate subject of one of Birkin’s twisted experiments. And of course, we get all the zombies, savage mutant dogs, and badly deformed monsters any fan of the original games could hope for.

Resident Evil: Welcome to Raccoon City opens exclusively in theaters on November 24, 2021. We strongly recommend only viewing movies in theaters if you have been fully vaccinated and wear a mask for the duration of the screening.

Listing image by Sony Pictures

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Don Everly of the Everly Brothers dies at 84

Don and Phil Everly, the Everly Brothers, performing at Hyde Park in 2004
Photo: Jo Hale (Getty Images)

Don Everly, the oldest and surviving member of the influential rock ‘n’ roll duo The Everly Brothers, died at his home in Nashville on Saturday. He was 84.

Don and Phil Everly, better known as The Everly Brothers, were among the most influential and groundbreaking groups of early rock ‘n’ roll. With their careers beginning within years of the genre’s founding, the heavenly harmonies of the Everlys, as heard on hits like “Bye Bye Love” and “Wake Up Little Susie,” found fans in The Beatles, The Beach Boys, Simon & Garfunkel, as well as millions of fans around the world. In addition to rock, their music helped popularize folk-rock and country-rock on the national stage.

Born on February 1, 1937, in Brownie, Kentucky, Issac Donald Everly grew up surrounded by music. After the family moved to Shenandoah, Iowa, his father, Ike, a former miner turned country musician, brought the boys to sing on his local radio program. Billed as “Little Donnie” and “Baby Boy Phil,” the Everly Brothers made their singing debut at ages 8 and 6.

In the 1950s, the group went from local radio singers to one of the biggest acts in the U.S. They signed to the independent New York label Cadence Records in 1957, the same year they released their first hit single, “Bye Bye Love,” which reached number two on the Billboard Pop Charts. By 1960, they had signed with Warner Bros. and were in the midst of a hot streak. Between 1957 and 1962, the Everlys had 15 top 10 hits, including “Bird Dog,” “Problems,” and the number-one hit “Cathy’s Clown.”

Their meteoric rise was not without its struggles, and the 1960s tested the group’s success. While the Everly Brothers scored five top 100 hits, the band would only return to the charts twice more throughout the decade. As the group’s popularity waned in an increasingly competitive field, both Don and Phil dealt with substance abuse issues. By the end of the decade, the band would release another seminal album: 1968’s Roots. Roots stood among other country-rock and folk-rock touchstones by The Byrds, Gram Parsons, and The Grateful Dead, a testament to the Everlys resilience and versatility. Nevertheless, Warners dropped the group in 1970.

The group broke up on stage at Knott’s Berry Farm in 1973 when Phil smashed his guitar on stage, leaving Don to tell the audience, “The Everly Brothers died 10 years ago.” However, they would return a decade later with the album EB ‘84, which featured the hit “On The Wings Of A Nightingale” written by Paul McCartney. Two years later, they joined Chuck Berry, James Brown, Elvis Presley, Sam Cooke, Jerry Lee Lewis, and more as members of the inaugural class of the Rock & Roll Hall Of Fame. Other accolades soon followed the Everlys, earning a lifetime achievement Grammy in 1997, for example.

In the early 2000s, the Everlys had all but finished recording music together. They toured with Simon & Garfunkel in 2003, but the Brothers’ schedule slowed significantly afterward, recording independently and sporadically throughout the decade.

On January 3, 2014, Phil Everly died of lung disease at the age of 74. Months after his death, Don told the L.A. Times, “I’m not over it. I really feel sad. I think about him every day. I always thought about him every day, even when we were not speaking to each other.”

But the Everlys impact was already set. Keith Richards called Don “one of the best rhythm guitarists in the world.” Paul McCartney said, “When John and I first started to write songs, I was Phil and he was Don.”

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