CD163+ perivascular macrophages in schizophrenia: a research framework for testing macrophage-related mechanisms

Elevated densities of CD163+ perivascular macrophages have been reported in schizophrenia post-mortem brain tissue, particularly in regions involved in neurodevelopment, dopaminergic signaling, and blood–brain barrier (BBB) regulation. However, the biological significance and developmental lineage of these findings remain unclear. While CD163 is linked to regulatory and scavenging functions, macrophage activation states form a continuum and cannot be inferred from any single marker. This Perspective outlines a structured, testable research framework to determine whether this accumulation reflects altered responsiveness to persistent intracellular, inflammatory, systemic, or treatment-related signals. To test this, we propose sequential methodological aims, including defining CD163+ cell localization and phenotypes in predefined brain regions, and assessing viral and non-viral molecular signals using spatial transcriptomic and cell-specific methods. This framework also involves comparing macrophage activation states across schizophrenia and other psychiatric and non-psychiatric control groups, using single-cell and single-nucleus sequencing. By not presuming a specific infectious aetiology, this approach will provide a general methodology to investigate macrophage-related mechanisms across diverse potential triggers. Within this model, HSV-1 is evaluated strictly as an illustrative proof-of-concept candidate for testing intracellular pathogen responses, rather than an exclusive cause, as epidemiological associations have been inconsistent and localization of viral materials within these cells has not been demonstrated. Similarly, Bacille Calmette–Guérin (BCG)-associated trained immunity is introduced strictly as a preliminary, ex vivo/in vitro approach to probe macrophage reprogramming and plasticity. Ultimately, this framework provides a systematic approach for investigating macrophage-related mechanisms and their potential drivers in schizophrenia without presupposing a specific underlying aetiology.

Physical education performance as a protective pathway: breaking the cycle between learning burnout and gaming disorder in Chinese adolescents

Background and AimsGaming disorder (GD) and learning burnout (LB) are critical issues impacting adolescents, with GD recognized by the World Health Organization as a behavioral addiction and LB contributing to academic disengagement. While prior research has examined bivariate relationships, such as GD’s negative correlation with academic performance and physical education performance, or LB’s association with poor grades, no study has integrated all four variables into one model to explore their dynamic interactions longitudinally.MethodsA cross-lagged panel network (CLPN) model was applied to longitudinal data from 811 Chinese middle school students collected at two time points.ResultsGD and LB showed minimal direct effects on academic performance or physical education performance. Instead, academic performance and physical education performance acted as protective factors, significantly alleviating LB, particularly among boys. These two protective factors were mutually reinforcing. Cognitive exhaustion (a core component of LB) and GD functioned as reciprocal risk factors.ConclusionInterventions for adolescent maladjustment should prioritize addressing learning burnout through academic and physical avenues rather than overemphasizing gaming disorder, with tailored strategies for different genders.

Circadian dimensions in insomnia disorder: mechanistic evidence, candidate phenotypes, and a phenotype-stratified research framework

Insomnia disorder is one of the most common sleep disorders and is traditionally conceptualized in terms of hyperarousal, altered sleep homeostasis, and cognitive-behavioral perpetuating factors. The two-process model of sleep regulation indicates that sleep initiation and maintenance depend not only on homeostatic sleep pressure but also on circadian phase, amplitude, and stability. Evidence suggests that some patients presenting with insomnia complaints have misalignment between endogenous circadian phase and the intended sleep window, whereas others show reduced rest-activity amplitude, increased sleep-timing variability, or abnormal light exposure patterns. This narrative review integrates clinical, measurement, mechanistic, and intervention evidence on circadian dimensions in insomnia disorder and proposes a candidate circadian phenotyping framework for future validation. The framework combines sleep diaries, actigraphy, light exposure assessment, dim-light melatonin onset (DLMO), and core body temperature rhythms to distinguish circadian rhythm sleep-wake disorder (CRSWD)-dominant insomnia complaints, insomnia disorder with circadian modifiers, and comorbid insomnia disorder and CRSWD. Cognitive behavioral therapy for insomnia (CBT-I) remains first-line treatment. Fixed wake time, morning light, evening light restriction, timed low-dose melatonin, scheduled activity, and multicomponent approaches are positioned as candidate adjunctive modules to be tested in phenotype-stratified trials. These phenotypes are not diagnostic categories, clinical decision algorithms, or treatment guidelines. The review instead translates circadian evidence in insomnia into testable propositions, including provisional phenotype definitions, recommended measurement strategies, falsifiable predictions, and future trial designs. Operational thresholds, reproducibility, predictive validity, incremental treatment benefit, optimal parameters, safety, implementation feasibility, and cost-effectiveness require prospective phenotype-stratified randomized trials and long-term follow-up.

The risk of weather data sabotage is rising

Every morning, airline dispatchers, grid operators, and farmers around the world make decisions based on the same thing: a weather forecast.

While these forecasts are something that most people glance at for two seconds, weather predictions influence major strategic decisions in many industries, with real money, livelihoods, and even actual lives at stake. Farmers use them to determine which crop variety to sow, when to fertilize, how much to invest in irrigation infrastructure, and how long livestock should graze. Utilities use them to decide where to build solar and wind farms, as well as how to price wholesale electricity. Predictions are used to warn people about extreme weather and to trigger emergency response measures. More recently, weather predictions have become relevant for an emerging industry: prediction markets, where people bet money on all kinds of real-world events, including the weather.

However, the temptation to manipulate weather data to get an edge in these markets, combined with a collective move toward data-driven AI weather forecasting, is starting to put the accuracy of weather predictions at risk. These risks are relatively manageable for now, but as experts in the field, we can foresee scenarios where they snowball into far bigger, more systemic problems. 

To develop weather predictions, we need accurate observations of current conditions. These are collected from several sources, including weather stations at airports, utilities, or transport services. Traditional operational systems like the Weather Research and Forecasting model or the European Centre for Medium-Range Weather Forecast (ECMWF) Integrated Forecasting System combine these observations with numerical approximations in order to estimate future weather patterns. 

Sometimes, weather stations have issues because of, for example, instrument failures or upgrades in equipment. These can be caught either in real time (through checking and correction) or retroactively. Traditional forecasting systems also have a built-in safeguard called data assimilation: Every incoming measurement is weighed against what the physical model says should be happening and against readings from nearby stations.

Together, these mechanisms help keep weather observations reliable and predictions robust. However, new threats are putting observational accuracy at risk. Earlier this year, news outlets reported that the weather station at Paris Charles de Gaulle Airport (CDG) had been manipulated to record suspicious temperature spikes on April 6 and April 15, 2026. Authorities speculate that a hand-held hairdryer or lighter might have come into play. Either way, it led to some big payouts for online prediction-market gamblers who had bet it would hit 22 °C (71.6 °F) on days when the actual average was around 18°C (64.4°F). One individual won $20,000.  

Fortunately, tampering with a single station like this can usually be caught by human monitoring or current statistical methods. In this case, members of a French climate nonprofit association noticed the anomalies by chance and raised the alarm.

But what if there are no human monitoring systems in place? And what about other types of manipulation? What if, instead of tampering with one station, someone remotely nudged the readings at many stations at once—making each change small enough to look plausible on its own? Existing quality controls struggle to catch this kind of coordinated manipulation. And time works against us; careful checks of data and metadata take hours or days, but forecasts have to go out on schedule, whatever the weather is doing.

The shift toward artificial intelligence in weather prediction raises the stakes. These methods are even more dependent on accurate, reliable weather observations; in fact, they are known as “data-driven models.” For example, researchers at ECMWF are exploring whether high-quality weather forecasts can be produced directly from raw observations, skipping the assimilation step that currently acts as a quality filter. Other researchers are going one step further; combining geospatial data (including weather station data) with large language models and agentic AI to support real-time, autonomous decision-making during extreme events such as storms. 

Possible benefits are improvements in accuracy, efficiency, and speed. But removing humans from the equation introduces a vast range of new risks.

At the low end of the risk scale, an individual speculator manipulates a weather station for personal gain—that is the CDG Airport case. One step up: A group of traders could coordinate to bias forecasts of renewable energy output, moving wholesale electricity prices and leaving whoever is on the other side of the trade holding the loss. And at the far end, a state actor or saboteur could manipulate one or many stations to set off an early warning system or even keep one silent when it should sound. Step by step, the risk grows, from fraud to compromised disaster preparedness to a matter of national security.  

As long as there are financial (or other) incentives to manipulate observational data, adversaries will search for new opportunities, and it is our task to stay one step ahead. Here are three ways.

1. Watch the stations. Data quality controls should include station security, anomaly detection and correction, and human oversight. Weather stations should be monitored continuously to deter tampering. Data homogenization methods that clean up weather records also need to get faster, with the goal of catching problems in real time. This will become increasingly important as agentic AI systems use these data to deliver real-time decisions. Finally, human oversight is needed to flag questionable data and model outcomes. After all, it was humans who caught the CDG Airport manipulation.

2. Protect the data to safeguard the AI. Data defense mechanisms must be positioned throughout the AI pipeline. AI explainability and adversarial robustness tools can help us understand the underlying data and the AI model outputs, help us identify data- or model-related issues, and potentially  make us more resilient to adversarial attacks. 

3. Ensure continuous accountability along the chain. Observational data passes through many hands: the operators who run the stations, the national weather services that steward the records, and the forecasting centers that turn them into predictions. No single one of them can protect data integrity alone—each guards its own link, and any anomaly needs to be communicated along the whole chain, from station operators to the people acting on the forecast.

It is fortunate that the situation at CDG Airport was caught, but it should serve as a wake-up call. As the role of observational data grows in weather forecasting, we need to adapt to evolving threats. This means protecting our data and models by strengthening existing oversight and accountability structures, and improving coordination among key partners.

This op-ed was written by:

  • Monique Kuglitsch — Innovation Manager at Fraunhofer Heinrich Hertz Institute and Chair of the UN Global Initiative on Resilience to Natural Hazards through AI Solutions
  • Jesper Dramsch — Scientist for Machine Learning at the European Centre for Medium-Range Weather Forecasts (ECMWF), where they work on AIFS (Artificial Intelligence Forecasting System), ECMWF’s data-driven weather prediction model
  • Franz G. Kuglitsch — Climate Scientist and Executive Secretary of the International Union of Geodesy and Geophysics (IUGG) at the GFZ Helmholtz Centre for Geosciences in Potsdam
  • Andrea Toreti — Senior Scientist at the European Commission’s Joint Research Centre (JRC), where he coordinates the European and Global Drought Observatory under the Copernicus Emergency Management Service

Opinion: MAHA is rewriting the vocabulary of American mental health care

At a May MAHA Institute summit organized around the theme of “overmedicalization,” the health secretary announced an action plan to promote psychiatric deprescribing. At first look, it seemed innocuous. The Substance Abuse and Mental Health Services Administration (SAMHSA) would study prescribing trends and publish fact sheets. Medicare would clarify how clinicians can be paid for the attentive work of tapering a patient off of a medication (which is already a part of routine clinical care). Webinars would teach prevention and “holistic” care. A technical expert panel would convene over the summer to make further recommendations. 

In reality, this announcement, and the steady stream of actions over the past 18 months, mark a quiet rewriting of the vocabulary of American mental health care — a massive rhetorical shift enacted while programs and protections that would actually solve the problem are dismantled.

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FLOAT for Healthcare PTSS

Conditions: Posttraumatic Stress Symptoms; Burnout; Burnout, Healthcare Workers; First Responders; PTSD; Healthcare Workforce Well-Being; Post-traumatic Stress Symptoms

Interventions: Behavioral: Floatation-REST; Behavioral: Documentary

Sponsors: Laureate Institute for Brain Research, Inc.

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Comparing Two Moral Injury Treatments

Conditions: Moral Injury

Interventions: Behavioral: Acceptance and Commitment Therapy for Moral Injury (ACT-MI); Behavioral: Present Centered Therapy for Moral Injury (PCT-MI)

Sponsors: VA Eastern Colorado Health Care System; Denver Research Institute; Northern California Institute of Research and Education; Henry M. Jackson Foundation for the Advancement of Military Medicine; Palo Alto Veterans Institute for Research

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