Iván Velásquez se refirió a la propuesta del presidente Gustavo Petro de establecer este viernes 19 de abril como n día cívico con el propósito de promover el ahorro del agua y la energía eléctrica

V takřka posvátné půdě, jen několik kilometrů od Bílého domu, je pohřbeno více než 400 tisíc padlých vojáků. A další stále přibývají. Význam hřbitova ještě zvyšuje každoroční ceremonie na Den obětí války. Navzdory nezpochybnitelné důležitosti pro Spojené státy je ale historie Arlingtonu protknutá nemalým počtem skandálů.  

"For this playlist, I’ve strung together some favorite songs that reflect the subject matter and themes of the stories and that serve as fuel for my creative process."

Bafana Bafana coach Hugo Broos has welcomed the number of young players who are given a chance and backed in the premier division, but has warned that to build on their progress, agents must prioritise players' development over their personal enrichment.

EJ Blanchette-Mackie
Jun 1, 1995; 36:1211-1226
Articles

Dawn L. Brasaemle
Dec 1, 2007; 48:2547-2559
Thematic Reviews

Saverio Cinti
Nov 1, 2005; 46:2347-2355
Research Articles

Sphingolipids have become established participants in the pathogenesis of obesity and its associated maladies. Sphingosine kinase 1 (SPHK1), which generates S1P, has been shown to increase in liver and adipose of obese humans and mice and to regulate inflammation in hepatocytes and adipose tissue, insulin resistance, and systemic inflammation in mouse models of obesity. Previous studies by us and others have demonstrated that global sphingosine kinase 1 KO mice are protected from diet-induced obesity, insulin resistance, systemic inflammation, and NAFLD, suggesting that SPHK1 may mediate pathological outcomes of obesity. As adipose tissue dysfunction has gained recognition as a central instigator of obesity-induced metabolic disease, we hypothesized that SPHK1 intrinsic to adipocytes may contribute to HFD-induced metabolic pathology. To test this, we depleted Sphk1 from adipocytes in mice (SK1^fatKO) and placed them on a HFD. In contrast to our initial hypothesis, SK1^fatKO mice displayed greater weight gain on HFD and exacerbated impairment in glucose clearance. Pro-inflammatory cytokines and neutrophil content of adipose tissue were similar, as were levels of circulating leptin and adiponectin. However, SPHK1-null adipocytes were hypertrophied and had lower basal lipolytic activity. Interestingly, hepatocyte triacylglycerol accumulation and expression of pro-inflammatory cytokines and collagen 1a1 were exacerbated in SK1^fatKO mice on a HFD, implicating a specific role for adipocyte SPHK1 in adipocyte function and inter-organ cross-talk that maintains overall metabolic homeostasis in obesity. Thus, SPHK1 serves a previously unidentified essential homeostatic role in adipocytes that protects from obesity-associated pathology. These findings may have implications for pharmacological targeting of the SPHK1/S1P signaling axis.

Guo-qiang Bi
Dec 15, 1998; 18:10464-10472
Articles

The GluN3A subunit of N-methyl-D-aspartate receptors (NMDARs) plays an established role in synapse development, but its contribution to neural circuits in the adult brain is less clear. Recent work has demonstrated that in select cell populations, GluN3A assembles with GluN1 to form GluN1/GluN3A receptors that are insensitive to glutamate and instead serve as functional excitatory glycine receptors (eGlyRs). Our understanding of these eGlyRs, and how they contribute to intrinsic excitability and synaptic communication within relevant networks of the developing and the mature brain, is only beginning to be uncovered. Here, using male and female mice, we demonstrate that GluN3A subunits are enriched in the adult ventral hippocampus (VH), where they localize to synaptic and extrasynaptic sites and can assemble as functional eGlyRs on CA1 pyramidal cells. GluN3A expression was barely detectable in the adult dorsal hippocampus (DH). We also observed a high GluN2B content in the adult VH, characterized by slow NMDAR current decay kinetics and a high sensitivity to the GluN2B-containing NMDAR antagonist ifenprodil. Interestingly, the GluN2B enrichment in the adult VH was dependent on GluN3A as GluN3A deletion accelerated NMDAR decay and reduced ifenprodil sensitivity in the VH, suggesting that GluN3A expression can regulate the balance of conventional NMDAR subunit composition at synaptic sites. Lastly, we found that GluN3A knock-out also enhanced both NMDAR-dependent calcium influx and NMDAR-dependent long-term potentiation in the VH. Together, these data reveal a novel role for GluN3A and eGlyRs in the control of ventral hippocampal circuits in the mature brain.

We used virus-mediated anterograde and retrograde tracing, optogenetic modulation, immunostaining, in situ hybridization, and patch-clamp recordings in acute brain slices to study the release mechanism and μ-opioid modulation of the dual glutamatergic/GABAergic inputs from the ventral tegmental area and supramammillary nucleus to the granule cells of the dorsal hippocampus of male and female mice. In keeping with previous reports showing that the two transmitters are released by separate active zones within the same terminals, we found that the short-term plasticity and pharmacological modulation of the glutamatergic and GABAergic currents are indistinguishable. We further found that glutamate and GABA release at these synapses are both virtually completely mediated by N- and P/Q-type calcium channels. We then investigated μ-opioid modulation of these synapses and found that activation of μ-opioid receptors (MORs) strongly inhibits the glutamate and GABA release, mostly through inhibition of presynaptic N-type channels. However, the modulation by MORs of these dual synapses is complex, as it likely includes also a disinhibition due to downmodulation of local GABAergic interneurons which make direct axo-axonic contacts with the dual glutamatergic/GABAergic terminals. We discuss how this opioid modulation may enhance LTP at the perforant path inputs, potentially contributing to reinforce memories of drug-associated contexts.

Plasticity in the subcortical motor basal ganglia–thalamo–cerebellar network plays a key role in the acquisition and control of long-term memory for new procedural skills, from the formation of population trajectories controlling trained motor skills in the striatum to the adaptation of sensorimotor maps in the cerebellum. However, recent findings demonstrate the involvement of a wider cortical and subcortical brain network in the consolidation and control of well-trained actions, including a brain region traditionally associated with declarative memory—the hippocampus. Here, we probe which role these subcortical areas play in skilled motor sequence control, from sequence feature selection during planning to their integration during sequence execution. An fMRI dataset (N = 24; 14 females) collected after participants learnt to produce four finger press sequences entirely from memory with high movement and timing accuracy over several days was examined for both changes in BOLD activity and their informational content in subcortical regions of interest. Although there was a widespread activity increase in effector-related striatal, thalamic, and cerebellar regions, in particular during sequence execution, the associated activity did not contain information on the motor sequence identity. In contrast, hippocampal activity increased during planning and predicted the order of the upcoming sequence of movements. Our findings suggest that the hippocampus preorders movements for skilled action sequences, thus contributing to the higher-order control of skilled movements that require flexible retrieval. These findings challenge the traditional taxonomy of episodic and procedural memory and carry implications for the rehabilitation of individuals with neurodegenerative disorders.

The precise regulation of Ca²⁺ signals plays a crucial role in the physiological functions of neurons. Here, we investigated the rapid effect of glucocorticoids on Ca²⁺ signals in cultured hippocampal neurons from both female and male rats. In cultured hippocampal neurons, glucocorticoids inhibited the spontaneous somatic Ca²⁺ spikes generated by Kv2.1-organized Ca²⁺ microdomains. Furthermore, glucocorticoids rapidly reduced the cell surface expressions of Kv2.1 and Ca_V1.2 channels in hippocampal neurons. In HEK293 cells transfected with Kv2.1 alone, glucocorticoids significantly reduced the surface expression of Kv2.1 with little effect on K⁺ currents. In HEK293 cells transfected with Ca_V1.2 alone, glucocorticoids inhibited Ca_V1.2 currents but had no effect on the cell surface expression of Ca_V1.2. Notably, in the presence of wild-type Kv2.1, glucocorticoids caused a decrease in the surface expression of Ca_V1.2 channels in HEK293 cells. However, this effect was not observed in the presence of nonclustering Kv2.1S586A mutant channels. Live-cell imaging showed that glucocorticoids rapidly decreased Kv2.1 clusters on the plasma membrane. Correspondingly, Western blot results indicated a significant increase in the cytoplasmic level of Kv2.1, suggesting the endocytosis of Kv2.1 clusters. Glucocorticoids rapidly decreased the intracellular cAMP concentration and the phosphorylation level of PKA in hippocampal neurons. The PKA inhibitor H89 mimicked the effect of glucocorticoids on Kv2.1, while the PKA agonist forskolin abrogated the effect. In conclusion, glucocorticoids rapidly suppress Ca_V1.2-mediated Ca²⁺ signals in hippocampal neurons by promoting the endocytosis of Kv2.1 channel clusters through reducing PKA activity.

Discover why scientists think we are in a new geologic age and what it means for our future.

Palworld developer Pocketpair has shared details from the patent infringement lawsuit brought against it by Nintendo and The Pokémon Company in September, shedding light on the plaintiffs’ demands. The two companies are seeking an injunction on Palworld, a survival game with monsters that bear alleged similarities to the creatures from the Pokémon franchise.

Xiaomi's new Android skin version — HyperOS 2.0 — was announced in China last month alongside the Xiaomi 15 series. While the company did not outline a rollout plan of its latest custom skin for devices in India, a new leak has hinted that the Poco X7 Pro will be the first to debut with HyperOS 2.0 in the country. The new Poco X series phone is rumoured to launch next month in India.

Epoch AI, a California-based research institute launched a new artificial intelligence (AI) benchmark last week. Dubbed FrontierMath, the new AI benchmark tests large language models (LLMs) on their capability of reseasoning and mathematical problem-solving. The AI firm claims that existing math benchmarks are not very useful due to factors like data contamination and AI models scoring very high scores on them.

It is definitely in the fitness of things that the Supreme Court in a most learned, laudable, landmark, logical and latest judgment titled Ramji Lal Bairwa & Anr vs State of Rajasthan & Ors in Criminal Appeal No. 3403 of 2023 (@ SLP (Crl.) No. 12912 of 2022) and cited in Neutral Citation No.: 2024 I

Read the in depth Review of POCO X2 Mobile Phones. Know detailed info about POCO X2 configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.

Read the in depth Review of Poco M3 Mobile Phones. Know detailed info about Poco M3 configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.

Read the in depth Review of POCO M5 Mobile Phones. Know detailed info about POCO M5 configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.

Read the in depth Review of Poco X5 Pro Mobile Phones. Know detailed info about Poco X5 Pro configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.

Read the in depth Review of Poco C51 Mobile Phones. Know detailed info about Poco C51 configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.

Read the in depth Review of Poco F5 Mobile Phones. Know detailed info about Poco F5 configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.

Read the in depth Review of POCO M6 Pro 5G Mobile Phones. Know detailed info about POCO M6 Pro 5G configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.

Geologists hoping to declare a new epoch dominated by humanity’s influence on Earth have chosen Crawford Lake in Canada as the location where the start of the Anthropocene is defined

Few volcanos come with more risk than Mexico's Popocatépetl, situated near Mexico City.  To mitigate danger, volcanologist Chiara Maria Petrone is trying to predict its next eruption

Scientific bodies are due to make an official decision in the coming year about whether to declare a new geochronological unit precipitated by the impact of humans on Earth

A proposal to define the Anthropocene, a geologic epoch defined by human activity, has been rejected – surprising even scientists who consulted the voting group

Humans are drastically changing the planet and the Anthropocene is a useful tool to help us deal with that – so let's stop quibbling over definitions

A proposal to define the Anthropocene as a geological epoch was rejected this March, but humanity's impact on Earth is real, whether formalised or not, says Jan Zalasiewicz

Title: Despite Pockets of Resistance, Most U.S. Kids Getting Vaccinated
Category: Health News
Created: 8/27/2015 12:00:00 AM
Last Editorial Review: 8/28/2015 12:00:00 AM

Memory formation is contingent on molecular and structural changes in neurons in response to learning stimuli—a process known as neuronal plasticity. The initiation step of mRNA translation is a gatekeeper of long-term memory by controlling the production of plasticity-related proteins in the brain. The mechanistic target of rapamycin complex 1 (mTORC1) controls mRNA translation, mainly through phosphorylation of the eukaryotic initiation factor 4E (eIF4E)-binding proteins (4E-BPs) and ribosomal protein S6 kinases (S6Ks). mTORC1 signaling decreases throughout brain development, starting from the early postnatal period. Here, we discovered that in mice, the age-dependent decrease in mTORC1 signaling occurs selectively in excitatory but not inhibitory neurons. Using a gene conditional knockout (cKO) strategy, we demonstrate that either up- or downregulating the mTORC1-4E-BP2 axis in GAD65 inhibitory interneurons, but not excitatory neurons, results in long-term object recognition and object location memory deficits. Our data indicate that the mTORC1 pathway in inhibitory but not excitatory neurons plays a key role in memory formation.

Nintendo and The Pokémon Company in September filed a patent infringement lawsuit against Palworld developer Pocketpair. 

At the time Nintendo did not share which patents Palworld infringed on, however, Pocketpair has now revealed what patents Nintendo are claiming were infringed on.

"As announced on September 19, 2024, The Pokémon Company and Nintendo Co Ltd (hereinafter referred to as the Plaintiffs) have filed a patent infringement lawsuit against us," said Pocketpair. "We have received inquiries from various media outlets regarding the status of the lawsuit, and we would like to report the details and current status of this case as follows.

"The Plaintiffs claim that Palworld, released by us on January 19, 2024, infringes upon the following three patents held by the Plaintiffs, and are seeking an injunction against the game and compensation for a portion of the damages incurred between the date of registration of the patents and the date of filing of this lawsuit."

Nintendo and The Pokémon Company are each seeking an injunction and damages of five million yen plus late payment damages.

Pocketpair added, "We will continue to assert our position in this case through future legal proceedings. Please note that we will refrain from responding individually to inquiries regarding this case. If any matters arise that require public notice, we will announce them on our website, etc."

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012 and taking over the hardware estimates in 2017. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel. You can contact the author on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/463022/nintendo-and-the-pokemon-company-seeking-injunction-and-damages-from-pocketpair/

The Pokémon series is no stranger to mobile games, being responsible for one of the most successful ever (Pokémon Go), as well as many others with different takes on the massive franchise, but this time it’s a Pokémon card game - a tradition nearly as old as the original games - that has taken the spotlight in Pokémon TCG Pocket.

For the physical version of Pokémon TCG, the collecting has always been as big or bigger than the battling, and right off the bat we can see that TCG Pocket has made plenty of room for both these aspects in its design. In fact, the battling isn’t even available until you level up a few times, which, while a bit limiting, is a fine way for players to get their bearing and collect a few cards before they start competing. The game does suffer from just a tad bit too much forced tutorialization in the early stages, particularly when getting to the battles, but it’s still hardly the worst sinner among mobile titles in this regard.

The collecting all starts with the opening of packs, an infamously addictive part of any card game, and they’ve done a good job of making the process quite satisfying TCG Pocket. More importantly, the number of packs given for free is quite generous - at least two packs a day by default - meaning the game is perfectly playable without spending money, regardless of whether you’re in it for the collecting or battling aspect. Whenever you obtain new cards, they also get filled out in a sort of card Pokédex, which adds to the fun of collecting new ones.

A lot of what makes the collecting in TCG Pocket enjoyable, however, is quite simply the excellent card art. This is, of course, borrowed mostly from the game’s physical counterpart, and strengthened by little touches like being able to being able to zoom in and tilt the cards, with a slight holographic on the rarer ones. Whether they’re cute or cool, the Pokémon themselves are at the heart of this franchise and with the generally splendid art the game does a great job of bringing them to life, in some ways doing them more justice than recent mainline entries with low-detailed 3D models.

As for the other part of aesthetics, namely sound design, the game is also passable in this area but nothing special with slightly boring battle music. It's not the biggest issue perhaps, as most are likely to play mobile games with sound disabled, but with all the cosmetic unlockables (which we shall get to) it   seems like a wasted opportunity not to have unlockable battle themes when the Pokémon series has so many great ones to draw upon from its legacy.

Looking for a moment at the less positive side, while Pokémon TCG Pocket is fairly generous to free-to-play players, it does still suffer from some of the pitfalls that are typical of that type of mobile game; namely, the amount of noise that comes with too many currencies, constant quests and rewards, and perhaps a few more types of cosmetics than is necessary. Again, I wouldn't describe Pokémon TCG Pocket as the worst sinner of this type of issue, mostly just that it can be a bit overwhelming at first, and of course knowing that it’s intended to add to the addictiveness of the game can be a bit iffy, but ultimately it isn’t too hard to ignore aspects you don’t care about and simply enjoy the ones you do.

It might be high time to touch on the battles themselves, which to many players might be their first encounter ever with the actual rules of these pretty collectible cards. While it might not be simplest card game ever invented, I’m happy to say the TCG Pocket variant is still intuitive, fun, and quite strategic once you get the hang of it. To summarize it in very brief: you play and evolve Pokémon from your hand onto the field and charge them up with energy types to allow them to attack. Just like in the RPGs, only one Pokémon is active at a time and can use one move per turn, while you can assign others to your “bench”, where they await their turn in the spotlight. Unlike in the RPGs, switching Pokémon won’t cost you your turn (only some energy), meaning benched Pokémon can potentially step into action immediately - if you have the energy necessary. Rather than any form of life-points, you win the battle by defeating three of your opponents' Pokémon, which each award one point.

This bench system and charging up of your Pokémon before they can take action might in some regards make the game slower compared to other card games, but it also adds a strategic element, since you can generally see what moves you and your opponent have available in the immediate future and can only really be caught by surprise by item or support cards (which can be quite useful but rarely complete game changers). It’s not the type of game where you perform crazy one-turn game-winning combos, but it’s fun for the strategic aspect and of course the satisfaction that comes from evolving your Pokémon throughout the battle - and sometimes pulling off an impressive comeback.

Adding to this are the EX-cards, extra powerful cards that come with the added risk of rewarding the opponent two points if defeated rather than one. I’ve seen complaints that this risk is too big in a game when it only takes three points to win (unlike the physical version of the game where you need six points), but when the card is extra strong and you have the option of switching it out it seems justified, plus you still have that golden window of playing it when your opponent already has two points, at which point the extra risk is nullified.

Ultimately there is one distinct issue with the battle system, however, which is how type weaknesses are handled. Pokémon TCG, whether physical or digital, has condensed Pokémon down to nearly half as many types (a tad too few in my opinion, though all 18 would definitely have been overwhelming), while the weaknesses and resistances are reduced to one type per card, and in TCG Pocket resistances are removed so you only have the weaknesses. This, for example, means that (most) Water types are weak to Lightning   but not Grass, while Fire types are weak to Water but not Ground (which has been combined with Fighting). The issue however is not so much the differences from the RPGs as it is simply having these basic and pretty consistent weaknesses in a game that, unfortunately, strongly encourages mono-type   decks in its design (or one type + colorless), since you’ll be needing specific energy types to charge your Pokémon and receive them at random if your deck uses multiple types.

While there is something to be said for having to commit to certain types, it’s a bit unfortunate that it’s taken to the degree where dual-type decks can feel awkward and triple-type decks, while allowed, require very specific cards or a lot of luck to pull off. The result is that when most players play with only one type and all types have one weakness, online matches will often either play out without weaknesses playing any role or with one player having an advantage before the first card is even played. One can always hope that this is somehow redesigned a bit in the future, but for now it’s an unfortunate though not game-breaking issue, as the weaknesses are at least a bit milder here, adding only a flat amount of damage rather than a multiplier.

Lastly it wouldn't review this game without mentioning the nostalgic aspect, which to many a player might add an extra appeal to the experience. Even as someone who hasn't dabbled in Pokémon cards for nearly 20 years, I can still recognize many that I’ve owned myself at some point, and it’s also great to revisit the first generation, which has smartly put front and center for now (with a small mix from other generations on top). I consider it a good call to start off with a single set of a manageable size for now - one that doesn’t seem too daunting - while leaving plenty of room to grow in the future.

All in all, Creatures Inc. and Dena Co. have done a great job adapting the Pokémon card game to mobile in a way that can appeal to both old and new players, and to those who want to collect and those who want to battle. It brings Pokémon to life with great card art and, contrary to unfortunate trends, the game is also fairly generous to its free-to-play players (and certainly a cheaper alternative to collecting the physical cards). While it does suffer from a few design issues and some classic pitfalls, it’s overall one of the better mobile games out there at the moment and certainly worth checking out for those who have nostalgia for the Pokémon TCG or old school Pokémon in general.

Full Article - https://www.vgchartz.com/article/463039/pokemon-tcg-pocket-android/

The Real Housewives of Salt Lake City is TV’s best soap opera, week after week offering twists more shocking than secret twins and characters returning from the dead. That’s because it’s all real, happening in the most haunted suburb in the continental United States.

Where else do two women connect over knowing the long-lost birth father of one’s child? Is there another city where women squabble over body positivity in a parking lot off the side of a snowy mountain? Surely, there’s no other place on Earth where Lisa Barlow could come across anywhere near a voice of reason.

But that all happens here in Salt Lake City. Five episodes in, Season 5 has continued to evolve into the most captivating season in modern Real Housewives history, carried by the ever-changing bonds between our OGs and a team of wonderfully bizarre newbies.

Read more at The Daily Beast.

Palworld developers Pocketpair have finally revealed which patents Nintendo and the Pokémon Company are suing them about. It looks like they're focusing on the act of throwing capsular items to catch or release monsters, together with the usage of monsters as mounts.

If you've somehow yet to encounter Palworld, it's a bestselling survival game that takes hefty - some would say, scandalous - inspiration from Pokémon, with players poaching Pokésque critters using magic spheres, and deploying them as soldiers and minions.

Read more

Stock and bond markets are already reacting in anticipation of the changes

Nintendo just announced that Animal Crossing: Pocket Camp (Free) is shutting down on November 28th at 3 PM UTC. Animal …

Continue reading "‘Animal Crossing: Pocket Camp’ Shutting Down This November, New Paid Game Set To Release With Save Transfer"

Nearly every day since she was a child, Alex Leow, a psychiatrist and computer scientist at the University of Illinois Chicago, has played the piano. Some days she plays well, and other days her tempo lags and her fingers hit the wrong keys. Over the years, she noticed a pattern: How well she plays depends on her mood. A bad mood or lack of sleep almost always leads to sluggish, mistake-prone music.

In 2015, Leow realized that a similar pattern might be true for typing. She wondered if she could help people with psychiatric conditions track their moods by collecting data about their typing style from their phones. She decided to turn her idea into an app.

After conducting a pilot study, in 2018 Leow launched BiAffect, a research app that aims to understand mood-related symptoms of bipolar disorder through keyboard dynamics and sensor data from users’ smartphones. Now in use by more than 2,700 people who have volunteered their data to the project, the app tracks typing speed and accuracy by swapping the phone’s onscreen keyboard with its own nearly identical one.

The software then generates feedback for users, such as a graph displaying hourly keyboard activity. Researchers get access to the donated data from users’ phones, which they use to develop and test machine learning algorithms that interpret data for clinical use. One of the things Leow’s team has observed: When people are manic—a state of being overly excited that accompanies bipolar disorder—they type “ferociously fast,” says Leow.

Compared to a healthy user [top], a person experiencing symptoms of bipolar disorder [middle] or depression [bottom] may use their phone more than usual and late at night. BiAffect measures phone usage and orientation to help track those symptoms. BiAffect

BiAffect is one of the few mental-health apps that take a passive approach to collecting data from a phone to make inferences about users’ mental states. (Leow suspects that fewer than a dozen are currently available to consumers.) These apps run in the background on smartphones, collecting different sets of data not only on typing but also on the user’s movements, screen time, call and text frequency, and GPS location to monitor social activity and sleep patterns. If an app detects an abrupt change in behavior, indicating a potentially hazardous shift in mental state, it could be set up to alert the user, a caretaker, or a physician.

Such apps can’t legally claim to treat or diagnose disease, at least in the United States. Nevertheless, many researchers and people with mental illness have been using them as tools to track signs of depression, schizophrenia, anxiety, and bipolar disorder. “There’s tremendous, immediate clinical value in helping people feel better today by integrating these signals into mental-health care,” says John Torous, director of digital psychiatry at Beth Israel Deaconess Medical Center, in Boston. Globally, one in 8 people live with a mental illness, including 40 million with bipolar disorder.

These apps differ from most of the more than 10,000 mental-health and mood apps available, which typically ask users to actively log how they’re feeling, help users connect to providers, or encourage mindfulness. The popular apps Daylio and Moodnotes, for example, require journaling or rating symptoms. This approach requires more of the user’s time and may make these apps less appealing for long-term use. A 2019 study found that among 22 mood-tracking apps, the median user-retention rate was just 6.1 percent at 30 days of use.

App developers are trying to avoid the pitfalls of previous smartphone-psychiatry startups, some of which oversold their capabilities before validating their technologies.

But despite years of research on passive mental-health apps, their success is far from guaranteed. App developers are trying to avoid the pitfalls of previous smartphone psychiatry startups, some of which oversold their capabilities before validating their technologies. For example, Mindstrong was an early startup with an app that tracked taps, swipes, and keystrokes to identify digital biomarkers of cognitive function. The company raised US $160 million in funding from investors, including $100 million in 2020 alone, and went bankrupt in February 2023.

Mindstrong may have folded because the company was operating on a different timeline from the research, according to an analysis by the health-care news website Stat. The slow, methodical pace of science did not match the startup’s need to return profits to its investors quickly, the report found. Mindstrong also struggled to figure out the marketplace and find enough customers willing to pay for the service. “We were first out of the blocks trying to figure this out,” says Thomas Insel, a psychiatrist who cofounded Mindstrong.

Now that the field has completed a “hype cycle,” Torous says, app developers are focused on conducting the research needed to prove their apps can actually help people. “We’re beginning to put the burden of proof more on those developers and startups, as well as academic teams,” he says. Passive mental-health apps need to prove they can reliably parse the data they’re collecting, while also addressing serious privacy concerns.

Passive sensing catches mood swings early

A crucial component of managing psychiatric illness is tracking changes in mental states that can lead to more severe episodes of the disease. Bipolar disorder, for example, causes intense swings in mood, from extreme highs during periods of mania to extreme lows during periods of depression. Between 30 and 50 percent of people with bipolar disorder will attempt suicide at least once in their lives. Catching early signs of a mood swing can enable people to take countermeasures or seek help before things get bad.

But detecting those changes early is hard, especially for people with mental illness. Observations by other people, such as family members, can be subjective, and doctor and counselor sessions are too infrequent.

That’s where apps come in. Algorithms can be trained to spot subtle deviations from a person’s normal routine that might indicate a change in mood—an objective measure based on data, like a diabetic tracking blood sugar. “The ability to think objectively about my own thinking is really key,” says retired U.S. major general Gregg Martin, who has bipolar disorder and is an advisor for BiAffect.

The data from passive sensing apps could also be useful to doctors who want to see objective data on their patients in between office visits, or for people transitioning from inpatient to outpatient settings. These apps are “providing a service that doesn’t exist,” says Colin Depp, a clinical psychologist and professor at the University of California, San Diego. Providers can’t observe their patients around the clock, he says, but smartphone data can help close the gap.

Depp and his team have developed an app that uses GPS data and microphone-based sensing to determine the frequency of conversations and make inferences about a person’s social interactions and isolation. The app also tracks “location entropy,” a metric of how much a user moves around outside of routine locations. When someone is depressed and mostly stays home, location entropy decreases.

Depp’s team initially developed the app, called CBT2go, as a way to test the effectiveness of cognitive behavioral therapy in between therapy sessions. The app can now intervene in real time with people experiencing depressive or psychotic symptoms. This feature helps people identify when they feel lonely or agitated so they can apply coping skills they’ve learned in therapy. “When people walk out of the therapist’s office or log off, then they kind of forget all that,” Depp says.

Another passive mental-health-app developer, Ellipsis Health in San Francisco, uses software that takes voice samples collected during telehealth calls to gauge a person’s level of depression, anxiety, and stress symptoms. For each set of symptoms, deep-learning models analyze the person’s words, rhythms, and inflections to generate a score. The scores indicate the severity of the person’s mental distress, and are based on the same scales used in standard clinical evaluations, says Michael Aratow, cofounder and chief medical officer at Ellipsis.

Aratow says the software works for people of all demographics, without needing to first capture baseline measures of an individual’s voice and speech patterns. “We’ve trained the models in the most difficult use cases,” he says. The company offers its platform, including an app for collecting the voice data, through health-care providers, health systems, and employers; it’s not directly available to consumers.

In the case of BiAffect, the app can be downloaded for free by the public. Leow and her team are using the app as a research tool in clinical trials sponsored by the U.S. National Institutes of Health. These studies aim to validate whether the app can reliably monitor mood disorders, and determine whether it could also track suicide risk in menstruating women and cognition in people with multiple sclerosis.

BiAffect’s software tracks behaviors like hitting the backspace key frequently, which suggests more errors, and an increase in typing “@” symbols and hashtags, which suggest more social media use. The app combines this typing data with information from the phone’s accelerometer to determine how the user is oriented and moving—for example, whether the user is likely lying down in bed—which yields more clues about mood.

Ellipsis Health analyzes audio captured during telehealth visits to assign scores for depression, anxiety, and stress.Ellipsis Health

The makers of BiAffect and Ellipsis Health don’t claim their apps can treat or diagnose disease. If app developers want to make those claims and sell their product in the United States, they would first have to get regulatory approval from the U.S. Food and Drug Administration. Getting that approval requires rigorous and large-scale clinical trials that most app makers don’t have the resources to conduct.

Digital-health software depends on quality clinical data

The sensing techniques upon which passive apps rely—measuring typing dynamics, movement, voice acoustics, and the like—are well established. But the algorithms used to analyze the data collected by the sensors are still being honed and validated. That process will require considerably more high-quality research among real patient populations.

Greg Mably

For example, clinical studies that include control or placebo groups are crucial and have been lacking in the past. Without control groups, companies can say their technology is effective “compared to nothing,” says Torous at Beth Israel.

Torous and his team aim to build software that is backed by this kind of quality evidence. With participants’ consent, their app, called mindLAMP, passively collects data from their screen time and their phone’s GPS and accelerometer for research use. It’s also customizable for different diseases, including schizophrenia and bipolar disorder. “It’s a great starting point. But to bring it into the medical context, there’s a lot of important steps that we’re now in the middle of,” says Torous. Those steps include conducting clinical trials with control groups and testing the technology in different patient populations, he says.

How the data is collected can make a big difference in the quality of the research. For example, the rate of sampling—how often a data point is collected—matters and must be calibrated for the behavior being studied. What’s more, data pulled from real-world environments tends to be “dirty,” with inaccuracies collected by faulty sensors or inconsistencies in how phone sensors initially process data. It takes more work to make sense of this data, says Casey Bennett, an assistant professor and chair of health informatics at DePaul University, in Chicago, who uses BiAffect data in his research.

One approach to addressing errors is to integrate multiple sources of data to fill in the gaps—like combining accelerometer and typing data. In another approach, the BiAffect team is working to correlate real-world information with cleaner lab data collected in a controlled environment where researchers can more easily tell when errors are introduced.

Who participates in the studies matters too. If participants are limited to a particular geographic area or demographic, it’s unclear whether the results can be applied to the broader population. For example, a night-shift worker will have different activity patterns from those with nine-to-five jobs, and a city dweller may have a different lifestyle from residents of rural areas.

After the research is done, app developers must figure out a way to integrate their products into real-world medical contexts. One looming question is when and how to intervene when a change in mood is detected. These apps should always be used in concert with a professional and not as a replacement for one, says Torous. Otherwise, the app’s assessments could be dangerous and distressing to users, he says.

When mood tracking feels like surveillance

No matter how well these passive mood-tracking apps work, gaining trust from potential users may be the biggest stumbling block. Mood tracking could easily feel like surveillance. That’s particularly true for people with bipolar or psychotic disorders, where paranoia is part of the illness.

Keris Myrick, a mental-health advocate, says she finds passive mental-health apps “both cool and creepy.” Myrick, who is vice president of partnerships and innovation at the mental-health-advocacy organization Inseparable, has used a range of apps to support her mental health as a person with schizophrenia. But when she tested one passive sensing app, she opted to use a dummy phone. “I didn’t feel safe with an app company having access to all of that information on my personal phone,” Myrick says. While she was curious to see if her subjective experience matched the app’s objective measurements, the creepiness factor prevented her from using the app enough to find out.

Keris Myrick, a mental-health advocate, says she finds passive mental-health apps “both cool and creepy.”

Beyond users’ perception, maintaining true digital privacy is crucial. “Digital footprints are pretty sticky these days,” says Katie Shilton, an associate professor at the University of Maryland focused on social-data science. It’s important to be transparent about who has access to personal information and what they can do with it, she says.

“Once a diagnosis is established, once you are labeled as something, that can affect algorithms in other places in your life,” Shilton says. She cites the misuse of personal data in the Cambridge Analytica scandal, in which the consulting firm collected information from Facebook to target political advertising. Without strong privacy policies, companies producing mental-health apps could similarly sell user data—and they may be particularly motivated to do so if an app is free to use.

Conversations about regulating mental-health apps have been ongoing for over a decade, but a Wild West–style lack of regulation persists in the United States, says Bennett of DePaul University. For example, there aren’t yet protections in place to keep insurance companies or employers from penalizing users based on data collected. “If there aren’t legal protections, somebody is going to take this technology and use it for nefarious purposes,” he says.

Some of these concerns may be mediated by confining all the analysis to a user’s phone, rather than collecting data in a central repository. But decisions about privacy policies and data structures are still up to individual app developers.

Leow and the BiAffect team are currently working on a new internal version of their app that incorporates natural-language processing and generative AI extensions to analyze users’ speech. The team is considering commercializing this new version in the future, but only following extensive work with industry partners to ensure strict privacy safeguards are in place. “I really see this as something that people could eventually use,” Leow says. But she acknowledges that researchers’ goals don’t always align with the desires of the people who might use these tools. “It is so important to think about what the users actually want.”

This article appears in the July 2024 print issue as “The Shrink in Your Pocket.”

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