Culture

Senescent cells undergo an irreversible and permanent arrest of cell division and are hallmarks of both the aging process and multiple chronic diseases. Senescent cells - and more importantly the factors they secrete, known collectively as the senescence-associated secretory phenotype (SASP) - are widely accepted as drivers of aging and multiple age-related diseases.

A new study publishing on January 16 in the open-access journal PLOS Biology from Drs. Nathan Basisty, Judith Campisi, Birgit Schilling (Buck Institute for Research on Aging) and colleagues extensively profiles the SASP in human cells. They show that a core secreted protein "signature" of senescent cells is enriched with aging biomarkers found in human plasma.

The study utilizes a comprehensive and unbiased technique called mass spectrometry combined with bioinformatics to develop secreted protein signatures of senescent cells. The researchers' results show that the SASP is about ten-fold more complex than is currently appreciated, allowing them to propose new signatures of senescent cells - both 'core' signatures shared across all senescent cells and signatures that identify specific subsets of senescent cells.

Mouse studies have demonstrated that the targeted removal of senescent cells has beneficial effects on cardiac, vascular, metabolic, neurological, renal, pulmonary and musculoskeletal functions. Therefore, the selective elimination of senescent cells or inhibition of the SASP that they secrete are promising therapeutic approaches to treat age-related diseases in humans. Development of drugs that eliminate senescent cells, known as senolytics, or drugs that inhibit the SASP, known as senomorphics, requires molecular markers to assess the abundance of senescent cells. However, there are currently no simple reliable secreted biomarkers to measure the senescent cell burden in humans.

"We hope that these biomarker signatures will help us measure the burden of senescent cells in human biofluids, such as plasma, to aid the translation of senescence-targeted therapies into the clinic," says Dr Basisty. "We believe that the proteins secreted by senescent cells will also be important biomarkers for aging, neurodegenerative diseases, and other diseases marked by the presence of senescent cells."

Along with this study, the researchers launched the SASP Atlas, a curated database of proteins secreted by senescent cells. This resource can be used by others in the research community to identify proteins originating from senescent cells in their own research.

HOUSTON -- (Jan. 16, 2020) -- In a new study, U.S. and Austrian physicists have observed quantum entanglement among "billions of billions" of flowing electrons in a quantum critical material.

The research, which appears this week in Science, examined the electronic and magnetic behavior of a "strange metal" compound of ytterbium, rhodium and silicon as it both neared and passed through a critical transition at the boundary between two well-studied quantum phases.

The study at Rice University and Vienna University of Technology (TU Wien) provides the strongest direct evidence to date of entanglement's role in bringing about quantum criticality, said study co-author Qimiao Si of Rice.

"When we think about quantum entanglement, we think about small things," Si said. "We don't associate it with macroscopic objects. But at a quantum critical point, things are so collective that we have this chance to see the effects of entanglement, even in a metallic film that contains billions of billions of quantum mechanical objects."

Si, a theoretical physicist and director of the Rice Center for Quantum Materials (RCQM), has spent more than two decades studying what happens when materials like strange metals and high-temperature superconductors change quantum phases. Better understanding such materials could open the door to new technologies in computing, communications and more.

The international team overcame several challenges to get the result. TU Wien researchers developed a highly complex materials synthesis technique to produce ultrapure films containing one part ytterbium for every two parts rhodium and silicon (YbRh2Si2). At absolute zero temperature, the material undergoes a transition from one quantum phase that forms a magnetic order to another that does not.

At Rice, study co-lead author Xinwei Li, then a graduate student in the lab of co-author and RCQM member Junichiro Kono, performed terahertz spectroscopy experiments on the films at temperatures as low as 1.4 Kelvin. The terahertz measurements revealed the optical conductivity of the YbRh2Si2 films as they were cooled to a quantum critical point that marked the transition from one quantum phase to another.

"With strange metals, there is an unusual connection between electrical resistance and temperature," said corresponding author Silke Bühler-Paschen of TU Wien's Institute for Solid State Physics. "In contrast to simple metals such as copper or gold, this does not seem to be due to the thermal movement of the atoms, but to quantum fluctuations at the absolute zero temperature."

To measure optical conductivity, Li shined coherent electromagnetic radiation in the terahertz frequency range on top of the films and analyzed the amount of terahertz rays that passed through as a function of frequency and temperature. The experiments revealed "frequency over temperature scaling," a telltale sign of quantum criticality, the authors said.

Kono, an engineer and physicist in Rice's Brown School of Engineering, said the measurements were painstaking for Li, who's now a postdoctoral researcher at the California Institute of Technology. For example, only a fraction of the terahertz radiation shined onto the sample passed through to the detector, and the important measurement was how much that fraction rose or fell at different temperatures.

"Less than 0.1% of the total terahertz radiation was transmitted, and the signal, which was the variation of conductivity as a function of frequency, was a further few percent of that," Kono said. "It took many hours to take reliable data at each temperature to average over many, many measurements, and it was necessary to take data at many, many temperatures to prove the existence of scaling.

"Xinwei was very, very patient and persistent," Kono said. "In addition, he carefully processed the huge amounts of data he collected to unfold the scaling law, which was really fascinating to me."

Making the films was even more challenging. To grow them thin enough to pass terahertz rays, the TU Wien team developed a unique molecular beam epitaxy system and an elaborate growth procedure. Ytterbium, rhodium and silicon were simultaneously evaporated from separate sources in the exact 1-2-2 ratio. Because of the high energy needed to evaporate rhodium and silicon, the system required a custom-made ultrahigh vacuum chamber with two electron-beam evaporators.

"Our wild card was finding the perfect substrate: germanium," said TU Wien graduate student Lukas Prochaska, a study co-lead author. The germanium was transparent to terahertz, and had "certain atomic distances (that were) practically identical to those between the ytterbium atoms in YbRh2Si2, which explains the excellent quality of the films," he said.

Si recalled discussing the experiment with Bühler-Paschen more than 15 years ago when they were exploring the means to test a new class of quantum critical point. The hallmark of the quantum critical point that they were advancing with co-workers is that the quantum entanglement between spins and charges is critical.

"At a magnetic quantum critical point, conventional wisdom dictates that only the spin sector will be critical," he said. "But if the charge and spin sectors are quantum-entangled, the charge sector will end up being critical as well."

At the time, the technology was not available to test the hypothesis, but by 2016, the situation had changed. TU Wien could grow the films, Rice had recently installed a powerful microscope that could scan them for defects, and Kono had the terahertz spectrometer to measure optical conductivity. During Bühler-Paschen's sabbatical visit to Rice that year, she, Si, Kono and Rice microscopy expert Emilie Ringe received support to pursue the project via an Interdisciplinary Excellence Award from Rice's newly established Creative Ventures program.

"Conceptually, it was really a dream experiment," Si said. "Probe the charge sector at the magnetic quantum critical point to see whether it's critical, whether it has dynamical scaling. If you don't see anything that's collective, that's scaling, the critical point has to belong to some textbook type of description. But, if you see something singular, which in fact we did, then it is very direct and new evidence for the quantum entanglement nature of quantum criticality."

Si said all the efforts that went into the study were well worth it, because the findings have far-reaching implications.

"Quantum entanglement is the basis for storage and processing of quantum information," Si said. "At the same time, quantum criticality is believed to drive high-temperature superconductivity. So our findings suggest that the same underlying physics -- quantum criticality -- can lead to a platform for both quantum information and high-temperature superconductivity. When one contemplates that possibility, one cannot help but marvel at the wonder of nature."

Si is the Harry C. and Olga K. Wiess Professor in Rice's Department of Physics and Astronomy. Kono is a professor in Rice's departments of Electrical and Computer Engineering, Physics and Astronomy, and Materials Science and NanoEngineering and the director of Rice's Applied Physics Graduate Program. Ringe is now at the University of Cambridge.

Additional co-authors include Maxwell Andrews, Maximilian Bonta, Werner Schrenk, Andreas Limbeck and Gottfried Strasser, all of the TU Wien; Hermann Detz, formerly of TU Wien and currently at Brno University; Elisabeth Bianco, formerly of Rice and currently at Cornell University; Sadegh Yazdi, formerly of Rice and currently at the University of Colorado Boulder; and co-lead author Donald MacFarland, formerly of TU Wien and currently at the University at Buffalo.

The research was supported by the European Research Council (ERC-227378), the Army Research Office (W911NF-14-1-0496, W911NF-17-1-0259, W911NF-14-1-0525), the Austrian Science Fund (FWF-W1243, P29279-N27, P29296-N27), the European Union's Horizon 2020 program (824109-EMP), the National Science Foundation (DMR-1720595, DMR-1920740, PHY-1607611), the Robert A. Welch Foundation (C-1411), Los Alamos National Laboratory and Rice University.

RCQM leverages global partnerships and the strengths of more than 20 Rice research groups to address questions related to quantum materials. RCQM is supported by Rice's offices of the provost and the vice provost for research, the Wiess School of Natural Sciences, the Brown School of Engineering, the Smalley-Curl Institute and the departments of Physics and Astronomy, Electrical and Computer Engineering, and Materials Science and NanoEngineering.

The public should be wary of searching for probiotic information online as most webpages originate from unreliable sources and the health-benefit claims are often not supported by robust scientific evidence.

A new study, published in Frontiers in Medicine, cautions that while Google is adept at sorting the most reliable websites to the top of the list, the majority of websites providing information on probiotics are from commercial sources.

"Most webpages with information on probiotics are from commercial sources or news outlets but these provide the least complete information, in terms of not discussing potential side effects or regulatory issues," reports author Professor Pietro Ghezzi, from the Brighton and Sussex Medical School, UK.

"We also find many websites allude to benefits of probiotics in diseases for which there is not much high-level scientific evidence, other than in mice."

Probiotics are live organisms that, if research holds its promise, could be beneficial to health. There is a large US market for probiotics but less so in the EU, likely due to stricter regulation for health claims. Nevertheless, the market for probiotics continuously expands with the globalization of online sales.

Should we believe the hype?

Concerned that the public has unrealistic expectations about the beneficial effects of probiotics (bolstered by online claims and hype in the news), Ghezzi and his colleagues decided to assess the information that the public were exposed to when searching online.

"We assessed the first 150 webpages brought up by a Google search for "probiotics", recorded where they originated from and the diseases they mentioned. The scientific evidence for health benefits of probiotics against these diseases were then examined for scientific rigor," explains co-author Michel Goldman, a Professor at the Institute for Interdisciplinary Innovation in healthcare, Université libre de Bruxelles, Belgium.

The researchers used the Cochrane library - a database of clinical trials and meta-analyses of evidence-based medicine - to assess the strength of scientific evidence found online.

Goldman adds, "We also looked at how Google ranked these websites, as often the public will not go past the first ten results - these will therefore have a higher visibility and impact."

Beware of unreliable sources

News-outlets and commercial sources made up the majority of the 150 webpages and the analysis showed these were the least reliable, often not mentioning the side effects on immunocompromised individuals nor any regulatory issues. In addition, the findings of experiments on mice were used to make claims about probiotic benefits against disease in humans.

But it's not all bad news. Ghezzi explains that Google has developed very stringent criteria for ranking health-related websites, however, we should always question where the information originates from.

"Google prioritizes webpages containing more complete and scientifically robust information about probiotics, particularly health portals, and these are given a higher ranking than commercial websites. However, the fact that there is such a large amount of commercially-oriented information is problematic for consumers who are searching for honest answers."

Bottom Line: American cancer survivors, particularly those 64 years or younger, faced substantial medical financial hardship and sacrifices in spending, savings, or living situation, according to data from a survey.

Journal in Which the Study was Published: Cancer Epidemiology, Biomarkers, and Prevention, a journal of the American Association for Cancer Research

Author: Xuesong Han, PhD, senior principal scientist in Health Services Research at the American Cancer Society

Background: "As the number of cancer survivors grows, the costs of cancer treatments rise, and patient cost-sharing increases, there is a growing need for financial intervention at multiple levels to help cancer survivors minimize their risk of financial hardship," said Han. "We hope our findings will inform the development of future health policies and interventions in care delivery."

In the United States, the number of cancer survivors increased by 1.4 million people in the past three years, reaching more than 16.9 million as of January 1, 2019. The economic burden of cancer is significant for American cancer survivors: Previous studies have reported that as high as two-thirds of cancer survivors face medical financial hardship. However, few studies have examined the intensity of financial hardship across multiple domains, or sacrifices made as a result of cancer treatment and its longer-term effects.

How the Study Was Conducted: Han and colleagues identified cancer survivors from the 2016 Medical Expenditure Panel Survey (MEPS), a nationally representative survey that collected information on health insurance coverage, health care utilization and expenditures, and health conditions.

Participants detailed the effects of their cancer, cancer treatment, and how their cancer experience has affected their finances, health insurance coverage, and employment status. Financial hardships included problems paying medical bills, financial distress, or delaying or forgoing medical care due to cost concerns. Financial sacrifices due to cancer included changes in spending and use of savings as a result of cancer treatment and its lasting effects.

Because people over the age of 65 years are generally eligible for Medicare insurance coverage, Han and colleagues examined results for adult survivors under and over the age of 65.

Results: Of the 401 cancer survivors aged 18 to 64 years, 54 percent reported they had faced medical financial hardship as a result of cancer diagnosis and treatment, and 54 percent said they had made financial sacrifices in spending, savings, or their living situation. Nearly a quarter reported trouble paying medical bills, needing to borrow money, or filing for bankruptcy due to cancer diagnosis and treatment. More than 40 percent were worried about finances and almost 30 percent were worried about forgoing or delaying care because of cost concerns.

Of the 562 cancer survivors aged 65 years or older, medical financial hardship and sacrifices were less prevalent; 42 percent reported ever facing medical financial hardship, and 38 percent said they had made financial sacrifices.

Factors that were significantly associated with more intense financial hardship included low income and educational attainment, minority racial/ethnic status, comorbidity, lack of private insurance coverage, extended employment change, and recent cancer treatment.

Financial hardship has been linked to higher symptom burden and worse quality of life, and in extreme cases, such as bankruptcy, it is associated with an increased risk of death, Han explained.

Author's Comments: "Overall, health insurance coverage is critically important for cancer patients and survivors," said Han. "Even those who had private insurance coverage reported financial hardship, suggesting that the types of coverage and extent of patient cost-sharing are important too."

"Provisions of the Affordable Care Act that have expanded insurance coverage options, such as the Medicaid expansion, have been associated with reductions in financial hardship among cancer survivors in other studies," Han explained. "Employers can play a large role in mitigating hardship through flexible workplace accommodations such as availability of paid and unpaid sick leave, and supportive programs for both survivors and family members."

Study Limitations: The main limitations of the study were the potential for recall bias in the self-reported surveys and lack of data on clinical features of cancer stage and treatment. The researchers defined measures of insurance coverage, family income, and number of comorbidities as current estimates at survey time, however they defined measures of financial hardship and sacrifices as ever occurring.

Funding & Disclosures: The authors declare no conflict of interest.

Preaching sexual abstinence to youth was popular for a number of decades, but research repeatedly found that such educational messages fell short in their intended goals. Simply telling youth not to have sex failed to delay the initiation of sex, prevent pregnancies, or stop the spread of sexually-transmitted diseases. Since the advent of photo- and video-sharing via phones, children have received similar fear-based messages to discourage sexting - the sending or receiving of sexually explicit or sexually suggestive images (photos or video) usually via mobile devices. Unfortunately, messages of sexting abstinence don't seem to be reducing the prevalence of adolescents sharing nudes.

Consequently, in a new paper published in the Journal of Adolescent Health, researchers from Florida Atlantic University and the University of Wisconsin-Eau Claire, say that it is time to teach youth "safe" sexting.

"The truth is that adolescents have always experimented with their sexuality, and some are now doing so via sexting," said Sameer Hinduja, Ph.D., co-author and a professor in the School of Criminology and Criminal Justice within FAU's College for Design and Social Inquiry, and co-director of the Cyberbullying Research Center. "We need to move beyond abstinence-only, fear-based sexting education or, worse yet, no education at all. Instead, we should give students the knowledge they need to make informed decisions when being intimate with others, something even they acknowledge is needed."

Hinduja and co-author Justin Patchin, Ph.D., a professor of criminal justice at the University of Wisconsin-Eau Claire and co-director of the Cyberbullying Research Center, acknowledge that although participating in sexting is never 100 percent "safe" (just like engaging in sex), empowering youth with strategies to reduce possible resultant harm seems prudent.

Hinduja and Patchin collected (unpublished) data in April 2019 from a national sample of nearly 5,000 youth between the ages of 12 and 17, and found that 14 percent had sent and 23 percent had received sexually explicit images. These figures represent an increase of 13 percent for sending and 22 percent for receiving from what they previously found in 2016.

The authors do want youth to understand that those who sext open themselves up to possible significant and long-term consequences, such as humiliation, extortion, victimization, school sanction, reputational damage, and even criminal charges. But they also want youth who are going to do it anyway to exercise wisdom and discretion to prevent avoidable fallout.

"This is not about encouraging sexting behaviors, any more than sex education is about encouraging teens to have sex," said Hinduja. "It simply recognizes the reality that young people are sexually curious, and some will experiment with various behaviors with or without informed guidance, and sexting is no exception."

Hinduja and Patchin provide suggested themes encapsulated in 10 specific, actionable messages that adults can share with adolescents in certain formal or informal contexts after weighing their developmental and sexual maturity.

1. If someone sends you a sext, do not send it to -- or show -- anyone else. This could be considered nonconsensual sharing of pornography, and there are laws prohibiting it and which outline serious penalties (especially if the image portrays a minor).

2. If you send someone a sext, make sure you know and fully trust them. "Catfishing"-- where someone sets up a fictitious profile or pretends to be someone else to lure you into a fraudulent romantic relationship (and, often, to send sexts) -- happens more often than you think. You can, of course, never really know if they will share it with others or post it online, but do not send photos or video to people you do not know well.

3. Do not send images to someone who you are not certain would like to see it (make sure you receive textual consent that they are interested). Sending unsolicited explicit images to others could also lead to criminal charges.

4. Consider boudoir pictures. Boudoir is a genre of photography that involves suggestion rather than explicitness. Instead of nudes, send photos that strategically cover the most private of private parts. They can still be intimate and flirty but lack the obvious nudity that could get you in trouble.

5. Never include your face. Of course, this is so that images are not immediately identifiable as yours but also because certain social media sites have sophisticated facial recognition algorithms that automatically tag you in any pictures you would want to stay private.

6. Make sure the images do not include tattoos, birthmarks, scars, or other features that could connect them to you. In addition, remove all jewelry before sharing. Also, consider your surroundings. Bedroom pictures could, for example, include wall art or furniture that others recognize.

7. Turn your device's location services off for all of your social media apps, make sure your photos are not automatically tagged with your location or username, and delete any meta-data digitally attached to the image.

8. If you are being pressured or threatened to send nude photos, collect evidence when possible. Having digital evidence (such as screenshots of text messages) of any maliciousness or threats of sextortion will help law enforcement in their investigation and prosecution (if necessary) and social media sites in their flagging and deletion of accounts.

9. Use apps that provide the capability for sent images to be automatically and securely deleted after a certain amount of time. You can never guarantee that a screenshot was not taken, nor that another device was not used to capture the image without you being notified, but using specialized apps can decrease the chance of distribution.

10. Be sure to promptly delete any explicit photos or videos from your device. This applies to images you take of yourself and images received from someone else. Having images stored on your device increases the likelihood that someone -- a parent, the police, a hacker -- will find them. Possessing nude images of minors may have criminal implications. In 2015, for example, a North Carolina teen was charged with possessing child pornography, although the image on his phone was of himself.

Australia needs a new whooping cough vaccine to ensure our most vulnerable are protected from the emergence of superbug strains, new UNSW research has shown.

The current vaccine, widely used since 2000, targets three antigens in the bacteria of the highly contagious respiratory disease which can be fatal to infants.

All babies under six months old - in particular, newborns not protected by maternal immunisation - are at risk of catching the vaccine-preventable disease because they are either too young to be vaccinated or have not yet completed the three-dose primary vaccine course.

Australia's whooping cough epidemic from 2008 to 2012 saw more than 140,000 cases - with a peak of almost 40,000 in 2011 - and revealed the rise of evolving strains able to evade vaccine-generated immunity.

In a series of UNSW studies, with the latest published today in Vaccine, UNSW researchers took this knowledge further and showed, in a world-first discovery, that the evolving strains made additional changes to better survive in their host, regardless of that person's vaccination status. They also identified new antigens as potential vaccine targets.

First author and microbiologist Dr Laurence Luu, who led the team of researchers with Professor Ruiting Lan, said whooping cough's ability to adapt to vaccines and survival in humans might be the answer to its surprise resurgence despite Australia's high vaccination rates.

"We found the whooping cough strains were evolving to improve their survival, regardless of whether a person was vaccinated or not, by producing more nutrient-binding and transport proteins, and fewer immunogenic proteins which are not targeted by the vaccine," Dr Luu said.

"This allows whooping cough bacteria to more efficiently scavenge nutrients from the host during infection, as well as to evade the body's natural immune system because the bacteria are making fewer proteins that our body recognises.

"Put simply, the bacteria that cause whooping cough are becoming better at hiding and better at feeding - they're morphing into a superbug."

Dr Luu said it was therefore possible for a vaccinated person to contract whooping cough bacteria without symptoms materialising.

"So, the bacteria might still colonise you and survive without causing the disease - you probably wouldn't know you've been infected with the whooping cough bacteria because you don't get the symptoms," he said.

"Another issue with the vaccine is that immunity wanes quickly - so, we do need a new vaccine that can better protect against the evolving strains, stop the transmission of the disease and provide longer lasting immunity."

Vaccination still key but new vaccine needed

Prof Lan said while he would like to see a new vaccine developed and introduced in the next five to 10 years, the research team's important discovery did not render Australia's whooping cough vaccine redundant.

"It is critical that people are vaccinated to prevent the spread of whooping cough - the current vaccine is still effective for protecting against the disease - but new vaccines need to be developed in the long-term," Prof Lan said.

"We need more research to better understand the biology of the whooping cough bacteria, how they cause disease and what proteins are essential for the bacteria to cause infection, so that we can target these proteins in a new and improved vaccine.

"This will all help to future-proof new vaccines against the evolving whooping cough strains."

Dr Luu agreed it was crucial that Australia maintained its high vaccination coverage for whooping cough.

"Although the number of whooping cough cases has increased during the past decade, it's still nowhere near as high as what it was before the introduction of whooping cough vaccines," Dr Luu said.

"Therefore, we emphasise that Australia must maintain its high vaccination coverage to protect vulnerable newborns who are not protected by maternal immunity and cannot complete the three-dose primary vaccine course until they are six months old.

"So, vaccination is especially important for children, people who are in contact with children and pregnant women who need the vaccine to produce antibodies to protect their newborns from developing whooping cough in the first few weeks of life."

In addition to babies under six months having a high risk of catching the disease, the elderly, people living with someone who has whooping cough and people who have not had a booster in the past 10 years, are also most at risk.

Whooping cough is characterised by a "whooping" sound and sufferers find it difficult to breathe.

The disease is more common during spring and spreads when an infected person coughs or sneezes and other people breathe in the bacteria.

An analysis of cyclical changes in the light spectrum emitted by Proxima Centauri, the star closest to the Sun, suggests it may be orbited by a second planet. Mario Damasso and colleagues present data suggesting that this candidate planet orbits Proxima Centauri every 5.2 years and may be a "super-Earth", with a mass higher than Earth's, though much lower than that of the Solar System ice giants Uranus and Neptune. If its existence is confirmed, this planet may provide insights into how low-mass planets form around low-mass stars. It could also challenge models of how super-Earths are born; most are believed to form near the "snowline," the minimum distance from a star at which water can turn to solid ice, but the candidate planet's orbit lies far beyond this sweet spot. A previous study of Proxima Centauri using the Atacama Large Millimeter/submillimeter Array (ALMA)--an astronomical observatory in northern Chile--reported an unknown source of light spectrum signals that could belong to a second planet or may simply have been the product of a neighboring galaxy or an unrelated phenomenon. To better understand if the signal originated from another planet orbiting the star, Mario Damasso and colleagues analyzed a 17.5-year-long time series of high-precision radial velocities using an exoplanet detection method that tracks a star's light spectrum. If this spectrum oscillates between red and blue, it indicates that the star is moving towards and away from the Earth at regular intervals, a cycle usually caused by an orbiting body's presence. The researchers found that the signal occurs over a 1,900-day period, suggesting it is likely unrelated to cyclical shifts in the star's magnetic field. However, the authors emphasize that more evidence is needed to confirm their conclusion.

The brain is a sort of fortress, equipped with barriers designed to keep out dangerous pathogens. But protection comes at a cost: These barriers interfere with the immune system when faced with dire threats such glioblastoma, a deadly brain tumor for which there are few effective treatments.

Yale researchers have found a novel way to circumvent the brain's natural defenses when they're counterproductive by slipping immune system rescuers through the fortresses' drainage system, they report Jan. 15 in the journal Nature.

"People had thought there was very little the immune system could do to combat brain tumors," said senior corresponding author Akiko Iwasaki. "There has been no way for glioblastoma patients to benefit from immunotherapy."

Iwasaki is the Waldemar Von Zedtwitz Professor of Immunobiology and professor of molecular, cellular, and developmental biology and an investigator for the Howard Hughes Medical Institute.

While the brain itself has no direct way for disposing of cellular waste, tiny vessels lining the interior of the skull collect tissue waste and dispose of it through the body's lymphatic system, which filters toxins and waste from the body. It is this disposal system that researchers exploited in the new study.

These vessels form shortly after birth, spurred in part by the gene known as vascular endothelial growth factor C, or VEGF-C.

Yale's Jean-Leon Thomas, associate professor of neurology at Yale and senior co-corresponding author of the paper, wondered whether VEGF-C might increase immune response if lymphatic drainage was increased. And lead author Eric Song, a student working in Iwasaki's lab, wanted to see if VEGF-C could specifically be used to increase the immune system's surveillance of glioblastoma tumors. Together, the team investigated whether introducing VEGF-C through this drainage system would specifically target brain tumors.

The team introduced VEGF C into the cerebrospinal fluid of mice with glioblastoma and observed an increased level of T cell response to tumors in the brain. When combined with immune system checkpoint inhibitors commonly used in immunotherapy, the VEGF-C treatment significantly extended survival of the mice. In other words, the introduction of VEGF-C, in conjunction with cancer immunotherapy drugs, was apparently sufficient to target brain tumors.

"These results are remarkable," Iwasaki said. "We would like to bring this treatment to glioblastoma patients. The prognosis with current therapies of surgery and chemotherapy is still so bleak."

Astronomers from UCLA's Galactic Center Orbits Initiative have discovered a new class of bizarre objects at the center of our galaxy, not far from the supermassive black hole called Sagittarius A*. They published their research today in the journal Nature.

"These objects look like gas and behave like stars," said co-author Andrea Ghez, UCLA's Lauren B. Leichtman and Arthur E. Levine Professor of Astrophysics and director of the UCLA Galactic Center Group.

The new objects look compact most of the time and stretch out when their orbits bring them closest to the black hole. Their orbits range from about 100 to 1,000 years, said lead author Anna Ciurlo, a UCLA postdoctoral researcher.

Ghez's research group identified an unusual object at the center of our galaxy in 2005, which was later named G1. In 2012, astronomers in Germany made a puzzling discovery of a bizarre object named G2 in the center of the Milky Way that made a close approach to the supermassive black hole in 2014. Ghez and her research team believe that G2 is most likely two stars that had been orbiting the black hole in tandem and merged into an extremely large star, cloaked in unusually thick gas and dust.

"At the time of closest approach, G2 had a really strange signature," Ghez said. "We had seen it before, but it didn't look too peculiar until it got close to the black hole and became elongated, and much of its gas was torn apart. It went from being a pretty innocuous object when it was far from the black hole to one that was really stretched out and distorted at its closest approach and lost its outer shell, and now it's getting more compact again."

"One of the things that has gotten everyone excited about the G objects is that the stuff that gets pulled off of them by tidal forces as they sweep by the central black hole must inevitably fall into the black hole," said co-author Mark Morris, UCLA professor of physics and astronomy. "When that happens, it might be able to produce an impressive fireworks show since the material eaten by the black hole will heat up and emit copious radiation before it disappears across the event horizon."

But are G2 and G1 outliers, or are they part of a larger class of objects? In answer to that question, Ghez's research group reports the existence of four more objects they are calling G3, G4, G5 and G6. The researchers have determined each of their orbits. While G1 and G2 have similar orbits, the four new objects have very different orbits.

Ghez believes all six objects were binary stars -- a system of two stars orbiting each other -- that merged because of the strong gravitational force of the supermassive black hole. The merging of two stars takes more than 1 million years to complete, Ghez said.

"Mergers of stars may be happening in the universe more often than we thought, and likely are quite common," Ghez said. "Black holes may be driving binary stars to merge. It's possible that many of the stars we've been watching and not understanding may be the end product of mergers that are calm now. We are learning how galaxies and black holes evolve. The way binary stars interact with each other and with the black hole is very different from how single stars interact with other single stars and with the black hole."

Ciurlo noted that while the gas from G2's outer shell got stretched dramatically, its dust inside the gas did not get stretched much. "Something must have kept it compact and enabled it to survive its encounter with the black hole," Ciurlo said. "This is evidence for a stellar object inside G2."

"The unique dataset that Professor Ghez's group has gathered during more than 20 years is what allowed us to make this discovery," Ciurlo said. "We now have a population of 'G' objects, so it is not a matter of explaining a 'one-time event' like G2."

The researchers made observations from the W.M. Keck Observatory in Hawaii and used a powerful technology that Ghez helped pioneer, called adaptive optics, which corrects the distorting effects of the Earth's atmosphere in real time. They conducted a new analysis of 13 years of their UCLA Galactic Center Orbits Initiative data.

In September 2019, Ghez's team reported that the black hole is getting hungrier and it is unclear why. The stretching of G2 in 2014 appeared to pull off gas that may recently have been swallowed by the black hole, said co-author Tuan Do, a UCLA research scientist and deputy director of the Galactic Center Group. The mergers of stars could feed the black hole.

The team has already identified a few other candidates that may be part of this new class of objects, and are continuing to analyze them.

Ghez noted the center of the Milky Way galaxy is an extreme environment, unlike our less hectic corner of the universe.

"The Earth is in the suburbs compared to the center of the galaxy, which is some 26,000 light-years away," Ghez said. "The center of our galaxy has a density of stars 1 billion times higher than our part of the galaxy. The gravitational pull is so much stronger. The magnetic fields are more extreme. The center of the galaxy is where extreme astrophysics occurs -- the X-sports of astrophysics."

Ghez said this research will help to teach us what is happening in the majority of galaxies.

Other co-authors include Randall Campbell, an astronomer with the W.M. Keck Observatory in Hawaii; Aurelien Hees, a former UCLA postdoctoral scholar, now a researcher at the Paris Observatory in France; and Smadar Naoz, a UCLA assistant professor of physics and astronomy.

The research is funded by the National Science Foundation, W.M. Keck Foundation and Keck Visiting Scholars Program, the Gordon and Betty Moore Foundation, the Heising-Simons Foundation, Lauren Leichtman and Arthur Levine, Jim and Lori Keir, and Howard and Astrid Preston.

In July 2019, Ghez's research team reported on the most comprehensive test of Einstein's iconic general theory of relativity near the black hole. They concluded that Einstein's theory passed the test and is correct, at least for now.

Tokyo, Japan--Earthquakes are generally thought of as abrupt, violent events that last for only moments. However, movement of the Earth's tectonic plates is often less sudden and more sustained - slow earthquakes can last for hours, months, or even longer.

Researchers led by The University of Tokyo have discovered signals due to slow slip events with large amounts of slip along the Nankai Trough subduction zone just southeast of Japan, reported in a new study published in Science Advances.

Slow earthquakes such as these slow slip events are exceedingly difficult to detect using conventional seismological techniques, especially in offshore areas. However, because understanding slow earthquake events is essential for evaluating the risks posed by more violent seismic events like megathrust earthquakes, new methods have been developed to address this problem.

For this research, a Global Navigation Satellite System-Acoustic ranging (GNSS-A) combination technique was used to monitor changes in the absolute position of the seafloor. According to study first author Yusuke Yokota, "GNSS-A was first proposed in the 1980s, but has really been developed and applied over the last two decades for detection of slow earthquakes. This method combines satellite detection of movements at the sea surface with undersea data from an acoustic ranging system, and can reliably detect deformation of 5 cm or more in offshore areas."

Slip sites generally were detected below the shallow undersea interplate boundary of the trough, adjacent to regions with strong interplate coupling. Recurrent offshore slow slip event signals were detected in the Kii and Bungo Channel areas, and were correlated with strong activity of very low frequency seismic events.

Slow slip event signals were not clearly identified in the Tosa Bay or Enshu-nada regions, although this may have been a matter of insufficient resolution. However, their absence may also support the possibility that these are the main slip regions of the megathrust zone of the Nankai Trough.

"Differences in the features between these regions may be related to earthquake history and reflect different friction conditions," explains Dr. Yokota. "Detailed understanding of these friction conditions and how they relate spatiotemporally to megathrust earthquake events is essential for accurate earthquake simulation. Therefore, studying these newly discovered slow slip events in the Nankai Trough will contribute to earthquake disaster prevention and preparedness."

In addition to informing earthquake disaster research, these findings also shed light on the marine sedimentary environment and plate tectonics of the Nankai Trough.

Brightly coloured male songbirds not only have to attract the female's eye, but also make sure their sperm can last the distance, according to new research.

In the study, published today in the Royal Society journal Biology Letters, a team of scientists led by Dr Kate Durrant from the School of Life Sciences at the University of Nottingham, looked at how evolution shapes the plumage and the sperm cells of songbird species so that they mate successfully and pass on their genes.

Previous studies have focussed on a bird's appearance alone, but this is the first study that has looked at this together with the shape of the sperm, to understand if intense competition shapes both plumage (to compete before mating) and the sperm (to compete after mating).

The team looked at 278 species of song bird from around the world and a combination of data on their plumage and the shape of their sperm, to see how they have evolved to ensure successful mating.

The eye-catching plumage of some male songbirds has long been explained as a result of sexual selection: brighter males compete more successfully for mates, and leave more offspring, so evolution favours them. Female birds, by contrast, remain drab, because for them it is more important to be camouflaged on the nest.

How much competition for mates a male song bird faces varies between species, and depends on factors such as the number of available females, how dense the population is, and other things such as the structure of the vegetation they are in.

Dr Durrant said: "The intensity of sexual selection varies between species. If mate competition is really strong, not only are males really colourful and attractive, but they also need to have the best sperm too if they are going to compete."

The 'midpiece' in the bird's sperm produces energy-containing molecules, called ATP, to power movement. Previously, experts thought that if the sperm had a large midpiece, it produced a lot of ATP, and the sperm 'swam' really quickly and got to the egg first. Whilst this is true in some species, it is not always the case and it is more likely that a large midpiece allows the sperm to last longer, rather than swim faster.

Data on plumage from previous studies were used, together with data on the shape of sperm, for 278 species of song birds. The team found that males from species with more elaborate and colourful plumage, had longer sperm midpieces, which allows the sperm to last for a long time after the male mates with the female, who then stores it for when she is ready to release an egg.

"In a really competitive environment, lots of males are competing with each other for the female's attention, and there can be a high number that mate with the same female, and this is where sperm and how long it lasts is really important," said Dr Durrant.

"If a female bird mates with a number of males, she will keep the sperm until she is ready to release an egg. At this point, long-lived sperm can reactivate and fertilise the egg. So it is not enough to be colourful, you have to have the total package and produce sperm that can last.

"What we are seeing is what evolution has done to these species to solve the problem of competing for mates," adds Dr Durrant.

BIRMINGHAM, Ala. - In preclinical experiments, University of Alabama at Birmingham researchers have revealed a key missing piece of the Alzheimer's disease puzzle. That allowed proof-of-concept experiments -- using an existing drug -- that dramatically reduced Alzheimer's pathology and symptoms in two mouse models, potentially offering an immediate treatment for this devastating disease.

The research was published today in the journal Science Translational Medicine. It included human brain tissue analysis and longitudinal clinical data that supported the in vivo mouse model data.

"Our study provides translational insights into mechanisms underlying amyloid-beta protein toxicity, which may have strong implications for future drug design," said Qin Wang, M.D., Ph.D. "It identifies an amyloid-beta/G protein-coupled receptor interaction that represents an attractive, disease-specific therapeutic target for Alzheimer's disease."

Interestingly, the pathologic mechanism found may also explain the failure of numerous Alzheimer's clinical trials that targeted reduction of the culprit in Alzheimer's disease -- amyloid protein buildup in the brain.

At the UAB School of Medicine, Wang is professor in the Department of Cell, Developmental and Integrative Biology.

It is widely accepted, Wang says, that buildup of amyloid-beta oligomers in the brain acts as a trigger to induce pathological changes in tau protein, and that altered tau protein is the bullet that targets and kills neurons in Alzheimer's disease. However, the pathway connecting these two was unknown.

Wang and colleagues have found that amyloid-beta oligomers hijack norepinephrine signaling at brain neurons, which falsely redirects this signal to activate a kinase called GSK3-beta. That activated kinase enzyme, in turn, hyper-phosphorylates tau protein, making it toxic for neurons.

This rewiring of the norepinephrine signaling takes place at a cell membrane receptor on the surface of neurons called the alpha-2A adrenergic receptor. This receptor is part of a large family of G protein-coupled receptors that detect molecules outside of a cell and then activate an internal signal that causes a cellular response. While a certain concentration of amyloid-beta oligomers can activate GSK3-beta, the presence of norepinephrine vastly sensitized that activation by up to two orders of magnitude, Wang and colleagues found.

Thus, the UAB researchers speculate that nanomolar concentrations of amyloid-beta oligomers in human brains induce a pathogenic GSK3-beta/tau cascade at the earliest stages of Alzheimer's disease. This theory suggests why multiple clinical trials to reduce levels of amyloid-beta oligomers in Alzheimer's disease patients have failed -- they cannot reduce the amyloid levels to such low concentrations.

Study details

The alpha-2A adrenergic receptor normally works this way -- it has a binding site for the neurotransmitter norepinephrine, and that binding activates a signaling process that mobilizes the brain and body for action. The UAB researchers found that amyloid-beta oligomers bind to a separate site on the alpha-2A adrenergic receptor, distinct from the site for norepinephrine binding. This initiates the pathological hijacking.

Such binding at a second site is called allosteric binding. In G protein-coupled receptors, allosteric ligands are known to often alter signaling of the receptor as part of normal physiology. After the researchers realized the allosteric binding, they searched to see which kinase might be activated by that binding, which is how they identified GSK3-beta.

Some clinical data supports this mechanism. The researchers found that alpha-2A adrenergic receptor from the postmortem prefrontal cortexes of Alzheimer's disease patients had a significant increase in alpha-2A adrenergic receptor activity, compared with non-demented, low-pathology controls. Also, epidemiologic analysis of cases from the National Alzheimer's Coordinating Center showed that taking the drug clonidine -- an activator of alpha-2A adrenergic receptor used to lower blood pressure -- worsened cognitive function in patients with cognitive deficits. Furthermore, the adverse effects of clonidine were stronger in patients with more severe dementia. Clonidine usage had no effect on subjects with normal cognition.

Wang and colleagues tested an existing drug -- idazoxan -- in a mouse model of Alzheimer's. Idazoxan is an alpha-2A adrenergic receptor antagonist that has been under investigation in clinical trials for depression. The hypothesis was that idazoxan blockage of alpha-2A adrenergic receptor in the presence of amyloid-beta pathology would show therapeutic potential. That was borne out in Alzheimer's-model mice.

The mice were treated with idazoxan for eight weeks beginning at age 8 months, a point when amyloid-beta plaques are already present in the brain and alpha-2A adrenergic receptor shows enhanced activity. Compared with controls, the UAB researchers found that: 1) Idazoxan reversed hyperactivation of GSK3-beta in the mouse brains, giving additional support for the critical role of alpha-2A adrenergic receptor in mediating amyloid-beta-induced activation of GSK3-beta in vivo; 2) In the cerebral cortex of idazoxan-treated Alzheimer's-model mice, the extent of amyloid-beta load was lower, showing that blockage of alpha-2A adrenergic receptor slowed the progression of amyloid-beta pathology; 3) Idazoxan treatment decreased the density of inflammatory microglial cells, suggesting a reduction of neuroinflammation; 4) Idazoxan treatment reduced tau hyper-phosphorylation, suggesting that blockade of the alpha-2A adrenergic receptor effectively alleviated amyloid-beta-induced tau pathology; and 5) Idazoxan-treated Alzheimer's-model mice performed nearly as well as normal mice, and significantly better than untreated Alzheimer's-model mice, in two tests for cognitive function.

"These data collectively demonstrate that blocking norepinephrine signaling through the alpha-2A adrenergic receptor is an effective strategy to ameliorate pathological and cognitive deficits associated with amyloid-beta," Wang said.

"The alpha-2A adrenergic receptor blockers such as idazoxan have been developed for use in other disorders, and repurposing these drugs could be a potentially effective, readily available strategy for Alzheimer's disease treatment," Wang said. "In addition, our data suggest that the amyloid-beta/alpha-2A adrenergic receptor interaction is an attractive, disease-specific therapeutic target for Alzheimer's because the alpha-2A adrenergic receptor/GSK3-beta/tau cascade can be activated only in the presence of amyloid-beta oligomers."

"Directly targeting the allosteric amyloid-beta/alpha-2A adrenergic receptor interface would not interfere with normal alpha-2A adrenergic receptor functions," Wang said, "and therefore would be less likely to result in complications associated with an extended dosing period necessary for Alzheimer's disease treatment."

A stem cell transplant -- also called a bone marrow transplant -- is a common treatment for blood cancers, such as acute myeloid leukemia (AML). Such treatment can cure blood cancers but also can lead to life-threatening complications, including heart problems and graft-versus-host disease, in which new immune cells from the donor attack a patient's healthy tissues.

A new study from Washington University School of Medicine in St. Louis suggests that extremely rare, harmful genetic mutations present in healthy donors' stem cells -- though not causing health problems in the donors -- may be passed on to cancer patients receiving stem cell transplants. The intense chemo- and radiation therapy prior to transplant and the immunosuppression given after allow cells with these rare mutations the opportunity to quickly replicate, potentially creating health problems for the patients who receive them, suggests the research, published Jan. 15 in the journal Science Translational Medicine.

Among the concerns are heart damage, graft-versus-host disease and possible new leukemias.

The study, involving samples from patients with AML and their stem cell donors, suggests such rare, harmful mutations are present in surprisingly young donors and can cause problems for recipients even if the mutations are so rare as to be undetectable in the donor by typical genome sequencing techniques. The research opens the door to a larger study that will investigate these rare mutations in many more healthy donors, potentially leading to ways to prevent or mitigate the health effects of such genetic errors in patients receiving stem cell transplants.

"There have been suspicions that genetic errors in donor stem cells may be causing problems in cancer patients, but until now we didn't have a way to identify them because they are so rare," said senior author Todd E. Druley, MD, PhD, an associate professor of pediatrics. "This study raises concerns that even young, healthy donors' blood stem cells may have harmful mutations and provides strong evidence that we need to explore the potential effects of these mutations further."

Added co-author Sima T. Bhatt, MD, an assistant professor of pediatrics who treats pediatric patients with blood cancers at Siteman Kids at St. Louis Children's Hospital and Washington University School of Medicine: "Transplant physicians tend to seek younger donors because we assume this will lead to fewer complications. But we now see evidence that even young and healthy donors can have mutations that will have consequences for our patients. We need to understand what those consequences are if we are to find ways to modify them."

The study analyzed bone marrow from 25 adult patients with AML whose samples had been stored in a repository at Washington University. Samples from their healthy matched donors, who were unrelated to the patients, also were sequenced. The donors' samples were provided by the Center for International Blood and Marrow Transplant Research in Milwaukee.

The 25 AML patients were chosen because they each had had samples banked at four separate times: before the transplant, at 30 days post-transplant, at 100 days post-transplant, and one year post-transplant.

Druley co-invented a technique called error-corrected sequencing, to identify extremely rare DNA mutations that would be missed by conventional genome sequencing. Typical next-generation sequencing techniques can correctly identify a mutation that is present in one in 100 cells. The new method, which can distinguish between true mutations and mistakes introduced by the sequencing machine, allows the researchers to find true mutations that are extremely rare -- those present in as few as one in 10,000 cells.

The healthy donors ranged in age from 20 to 58, with an average age of 26. The researchers sequenced 80 genes known to be associated with AML, and they identified at least one harmful genetic mutation in 11 of the 25 donors, or 44%. They further showed that 84% of all the various mutations identified in the donors' samples were potentially harmful, and that 100% of the harmful mutations present in the donors later were found in the recipients. These harmful mutations also persisted over time, and many increased in frequency. Such data suggest the harmful mutations from the donor confer a survival advantage to the cells that harbor them.

"We didn't expect this many young, healthy donors to have these types of mutations," Druley said. "We also didn't expect 100% of the harmful mutations to be engrafted into the recipients. That was striking."

According to the researchers, the study raises questions about the origins of some of the well-known side effects of stem cell transplantation.

"We see a trend between mutations from the donor that persist over time and the development of chronic graft-versus-host disease," said first author Wing Hing Wong, a doctoral student in Druley's lab. "We plan to examine this more closely in a larger study."

Though the study was not large enough to establish a causal link, the researchers found that 75% of the patients who received at least one harmful mutation in the 80 genes that persisted over time developed chronic graft-versus-host disease. Among patients who did not receive mutations in the 80 genes, about 50% developed the condition. Because the study was small, this difference was not statistically significant, but it is evidence that the association should be studied more closely. In general, about half of all patients who receive a stem cell transplant go on to develop some form of graft-versus-host disease.

The most common mutation seen in the donors and the cancer patients studied is in a gene associated with heart disease. Healthy people with mutations in this gene are at higher risk of heart attack due to plaque buildup in the arteries.

"We know that cardiac dysfunction is a major complication after a bone marrow transplant, but it's always been attributed to toxicity from radiation or chemotherapy," Druley said. "It's never been linked to mutations in the blood-forming cells. We can't make this claim definitively, but we have data to suggest we should study that in much more detail."

Added Bhatt: "Now that we've also linked these mutations to graft-versus-host disease and cardiovascular problems, we have a larger study planned that we hope will answer some of the questions posed by this one."

Could feces offer hope to survivors of spinal cord injuries?

It's a question University of Alberta physical therapy researcher Karim Fouad never thought he'd ask. But the expert in spinal cord injuries said the digestive tract could help explain the link between spinal injuries and changes in mental health, such as increased anxiety and depression.

"You would think that if you have a stroke or spinal injury, 'no wonder you're depressed,'" said Fouad. "But it turns out there might be more to it than that."

In a new study, Fouad's team discovered that rats with spinal injuries experienced changes to their gut bacteria and a rise in anxiety-like behaviour. When rats with spinal injuries were given fecal transplants from healthy rats, their behaviour--and gut bacteria--remained normal.

Fouad suggests that bacteriotherapy, in the form of "poop pills," could one day be used to improve well-being following spinal cord injuries and diseases of the central nervous system.

"I think it has huge potential," Fouad said. "The beauty of it is that if this translates to humans, we'd have a simple tool that could potentially improve mental health."

Gut health

Researchers have long observed a deterioration of mental health following spinal cord injuries.

Patients who experience paralysis are at an increased risk of suicide. The increased prevalence of depression also means patients often miss their best window for recovery by losing interest in rehab, Fouad said, leading to a worse quality of life.

Connections between poor intestinal health and mental state have also been found outside of spinal cord research. Research at the U of A has even pointed to how gut health could help explain a disease like multiple sclerosis.

Fouad decided to test for similar connections on spinal cord injuries. When rats received minor spinal cord injuries, he observed a dramatic change in gut flora. It took up to four weeks for digestive tracts to return to normal.

To test anxiety-like behaviour, Fouad and his team also tested the rats on an elevated plus maze, gauging their willingness to risk venturing onto an exposed platform. Three weeks after recovery, injured rats remained far more reluctant to overcome their natural aversion to open spaces than the typical rats.

The next part of the experiment flipped those findings upside down. Some of the injured rats were given a fecal transplant. They made an astonishing recovery, becoming even more willing to venture out on the exposed platform.

"It's dramatic," said Fouad. "Diseases and injuries seem to trigger changes of the microbiome, and this can have much further effects."

Implications

Fouad hopes to test the effectiveness of fecal transplants over time, and to see whether anxiety could be induced simply by adding the wrong gut bacteria to animals raised in sterile environments.

He said there could be wider implications for these findings. Scientists often house animals together in experiments. But since rats are notorious omnivores--known to eat the feces of other rats--researchers may have inadvertently skewed thousands of experiments in which gut health was a potential modifying factor.

"How many generations of experiments have been done where microbiome changes were a potential influence and animals were eating the poo and maybe negating the effect?" Fouad said. "That's a scary thought."

Fecal transplants might not have the same allure as stem cells for spinal cord patients, Fouad said, but for patients facing a condition in which incremental gains can make a pivotal difference, poop pills could make a big difference.

"Is it going to cure spinal injury? No," he said. "But if you're in a wheelchair and dealing with it in a good mindset, it could make a big difference."

A new study finds that an interactive voice application using artificial intelligence is an effective way to monitor the wellbeing of patients being treated for serious mental illness.
Researchers from UCLA followed 47 patients for up to 14 months using an application called MyCoachConnect. All of the patients were being treated by physicians for serious mental illnesses, including bipolar disorder, schizophrenia and major depressive disorder.

For the study, published in PLOS ONE, participants called a toll-free number one or two times a week and answered three open-ended questions when prompted by a computer-generated voice. The questions were: How have you been over the past few days?; What's been troubling or challenging over the past few days?; and What's been particularly good or positive?

MyCoachConnect was designed to collect personalized patient responses, said lead author Dr. Armen Arevian, director of the Innovation Lab at the Jane and Terry Semel Institute for Neuroscience and Human Behavior. Specifically, the AI was trained to use an individual's own words to offer a personalized analysis for each patient. The application focused primarily on the choice of words the patients used in their responses, how their responses changed over time, with a smaller emphasis on audio features like tone of voice.

The analysis of the data, conducted in collaboration with researchers from USC's Signal Analysis and Interpretation Laboratory (SAIL), found that the application's analysis was as accurate at monitoring patients' mental states as their treating physicians

"The way people answer questions and the way they change their answers over time is unique to each patient," Arevian said. "We were looking at a person as a person and not as a diagnosis."

For the study, patients made calls either from a mobile phone, landline, or pay phone, and were asked to speak for two to three minutes for each question.

"Technology doesn't have to be complicated," Arevian said. "In this study, patients didn't need a smartphone or any a phone at all. It could be simple and low tech on the patient end, and high tech on the backend."

Researchers hope that artificial intelligence that can analyze data collected from apps such as MyCoachConnect will enable more proactive and personalized care for individuals. The application, for example, may help improve treatment by intervening early when someone is experiencing more symptoms.

"Artificial intelligence allowed us to illuminate the various clinically-meaningful dimensions of language use and vocal patterns of the patients over time and personalized at each individual level" said senior author Dr. Shri Narayanan, Niki and Max Nikias Chair in Engineering and Director of SAIL at the USC Viterbi School of Engineering.

Some participants were interviewed after the study ended, and said they found the system easy and enjoyable to use, Arevian said.

"They said speaking to a computer-generated voice allowed them to speak more freely," Arevian said. "They also said it helped them feel less lonely because they knew that someone would be listening to it, and to them that meant that someone cared."

MyCoachConnect was developed and hosted on the Chorus platform, which was developed by Arevian at UCLA and allows people to visually create mobile and other computer applications without computer programming in as little as a few minutes.