Over the past three decades, criteria for Empirically Supported Treatments (ESTs) have strengthened methodological rigor in psychotherapy research by prioritizing randomized controlled trials and systematic evidence synthesis. However, prevailing frameworks remain largely centered on efficacy under controlled conditions, offering limited operational guidance for integrating contextual factors that critically shape real-world effectiveness. We propose the Contextualized Empirically Supported Treatment Framework (C-EST), a normative and operational model that integrates certainty of evidence with structured appraisal of contextual domains essential for clinical decision-making, guideline development, and policy. Building on the Tolin criteria, GRADE, GRADE-CERQual, and the GRADE Evidence-to-Decision approach, C-EST embeds assessment of empirical certainty within five interconnected domains (1): empirical evidence (2), critical appraisal of the body of evidence, (3) functional and cultural impact, (4) contextual factors, including values, acceptability, feasibility, and equity, and (5) transparency and living evidence. Rather than relying on binary classifications (“supported” vs. “unsupported”), the framework enables nuanced judgments such as “supported with contextual concerns,” explicitly documenting boundaries of applicability. Using Cognitive Behavioral Therapy for depression and psychological interventions for postpartum depression as illustrative cases, we demonstrate how contextual appraisal refines, rather than weakens, established evidence classifications. By aligning internal validity with external, cultural, and equity relevance, C-EST transforms evidence evaluation from a static designation into a dynamic decision-support tool. Integrating contextual evidence is not an ethical add-on but a methodological imperative to ensure that psychological treatments are not only efficacious, but applicable, equitable, and responsive to diverse real-world mental health needs.
Non-invasive electrical stimulation for sleep disturbances in adults: protocol for an evidence−mapping umbrella review of systematic reviews and meta−analyses with subgroup analysis by intervention type and population
BackgroundSleep disturbances affect 10%–30% of adults worldwide. Non−invasive electrical stimulation (e.g., transcranial electrical stimulation) has emerged as a promising non−pharmacological intervention. Although numerous systematic reviews and meta−analyses have been published, they vary considerably in methodological quality, populations, intervention types, and conclusions. No umbrella review has yet synthesised the evidence across different modalities and populations. This evidence mapping umbrella review aims to systematically chart the existing systematic reviews, assess methodological quality, quantify overlap, and describe evidence patterns across diverse modalities and populations.MethodsFollowing JBI guidelines, we will search PubMed, Embase, Cochrane Database of Systematic Reviews, Web of Science, PsycINFO, and Scopus (inception to April 2026), restricted to English. Grey literature will be searched via PROSPERO, ClinicalTrials.gov, Google Scholar (first 200 records), and reference list screening (snowballing). We will include systematic reviews and meta−analyses of randomised controlled trials evaluating any non−invasive electrical stimulation for sleep outcomes. Two reviewers will independently screen, extract data, and assess methodological quality using AMSTAR 2. Primary study overlap will be quantified by the Corrected Covered Area. Where feasible, we will calculate 95% prediction intervals, perform Egger’s regression tests, and conduct excess significance tests using review-level summary estimates. Subgroup analyses will be stratified by intervention and population type. Sensitivity analyses will exclude: (1) reviews with critically low AMSTAR 2 ratings, (2) preprints, (3) reviews at high risk of reporting bias, and (4) studies where sleep is not the primary outcome. The primary outcome is subjective sleep quality; total sleep time is a key secondary outcome. Evidence will be graded using the Fusar−Poli classification, with GRADE for key outcomes.DiscussionThis umbrella review will provide the highest level of evidence synthesis, identifying modalities with more consistent or higher certainty evidence and highlighting areas where evidence remains uncertain. Limitations include restriction to English (which may disproportionately impact modalities such as TEAS), expected heterogeneity, and possible insufficient data for some subgroup analyses. All amendments have been documented in PROSPERO (CRD420261357590).Clinical Trial Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420261357590.
A bidirectional relationship between atrial fibrillation and depression: epidemiology, mechanisms, and clinical implications
Atrial fibrillation (AF) represents a common cardiac arrhythmia that carries substantial morbidity and mortality risks, whereas depression serves as a significant psychological factor affecting cardiovascular health. Recent findings underscore a reciprocal relationship between AF and depression, suggesting that depression may heighten the likelihood of developing AF, while AF may, in turn, worsen depressive symptoms. This review aims to provide a thorough examination of the epidemiological features that underpin this relationship, focusing on population-based research that clarifies prevalence rates and associated risk factors. Furthermore, it delves into the intricate biological and psychosocial mechanisms that connect these two conditions, which include dysregulation of the autonomic nervous system, inflammation, neurohormonal pathways, and behavioral influences. The clinical ramifications of this reciprocal association are also addressed, highlighting the necessity for integrated screening and management approaches to enhance patient outcomes. By consolidating existing research, this article seeks to enrich the understanding of the relationship between AF and depression, as well as to assist clinicians in optimizing therapeutic strategies tailored to address this dual burden.
Plasma microRNA signatures in drug-naïve Romanian adolescents with first-episode psychosis
Psychotic disorders are a group of severe psychiatric conditions with onset typically occurring in adolescence or early adulthood. Despite significant efforts to identify clinically useful candidates, no validated biomarkers for psychiatric disorders currently exist. The diagnosis of psychotic disorders is exclusively based on clinical assessment, significantly affected by individual differences and symptom overlap. Although circulating microRNAs (miRNAs) have emerged as potential peripheral biomarkers for early diagnosis and disease evolution, most studies concentrate on adult, medicated cohorts. Studies on miRNA profiles in drug-naïve adolescents with first-episode psychosis (FEP) are scarce. This study aims to identify the plasma miRNA profile in treatment-naïve Romanian adolescents with first-episode psychosis and to compare it with that of age- and sex-matched healthy controls. The plasma from 14 adolescents, seven drug-naïve FEP and seven and age-matched controls (CTRL) aged 15–18 years was collected. Psychiatric symptoms were assessed using PANSS, HAM-D, and YMRS scales. The levels of 179 miRNAs were assessed using qRT-PCR. A case-control analysis on miRNAs levels between FEP and CTRL was performed, as well as correlations with clinical measures. Twenty-one miRNAs showed significantly lower levels and two higher levels in FEP patients compared to controls. After adjustment for multiple comparisons, miR-125a-5p, miR-205-5p, miR-145-5p, miR-363-3p, and miR-23b-3p remained statistically significant (FDR<0.05). Notably, miR-125a-5p, miR-23b-3p, and miR-146a-5p levels negatively correlated with psychotic, depressive, and manic symptom severity, while miR-16-5p and miR-363-3p positively correlated with symptom scores. Comparison with previous studies indicated limited overlap, reflecting potential influences of age, treatment status, and genetic or environmental factors. This work demonstrates that Romanian treatment-naïve adolescents with first-episode psychosis had a unique circulating miRNA profile correlated with symptom severity, indicating their potential as early-stage biomarkers. The results underscore the necessity of accounting for age, treatment status, and environmental variables in the interpretation of miRNA modifications in psychotic illnesses.
Genetic–exposome interactions and aging clocks in dementia: the ReDLat2 initiative
Nature Medicine, Published online: 28 May 2026; doi:10.1038/s41591-026-04433-3
Genetic–exposome interactions and aging clocks in dementia: the ReDLat2 initiative
STAT+: Blood pressure tech floods the market after FDA relaxes wearables oversight
In early January, the Food and Drug Administration delivered on the Trump administration’s deregulatory promises by allowing more wellness products to be marketed without the agency’s authorization. Leaders at smart ring maker Oura swiftly planted the pivot foot.
“As soon as this guidance came out, literally the same day, we started having conversations with our product team around what our roadmap looks like, features that we could bring in and actually ship sooner,” Ricky Bloomfield, the company’s chief medical officer, told STAT less than a week after the FDA announcement. He added: “this guidance helps give us more confidence that we can release features sooner and not have to spend months getting additional clarification from the FDA.”
One thing FDA clarified in the updated guidance is that companies can release products that use sensors to “estimate, infer, or output” blood pressure and blood glucose readings without approval, if they are intended for wellness purposes. In a speech at the Consumer Electronics Show the day the guidance was announced, the FDA commissioner at the time, Marty Makary, said his agency would “get out of the way” of products that weren’t making medical or clinical claims. “This reduces the amount of subjectivity by regulators and guesswork by developers,” he said.
Five months later, consumer technology giants have already taken advantage. Oura on Thursday announced a refreshed model of its ring and a battery of new features, including two aimed at providing users with insights on blood pressure. In March, Samsung released a smartwatch feature that offers users readings of their systolic and diastolic blood pressure.
Elsewhere, upstart developers are racing to market with do-it-all devices. A smart ring called the Pin Pulse, which claims to offer readings of blood pressure, blood glucose, sleep insights, and more, raised $260,000 in a Kickstarter campaign that ended in April. The product was conceived by recent University of California, Berkeley graduate students who partially outsourced technical development to a team in China.
Optimistically, the new wave of blood pressure products may help raise awareness about a deadly hypertension epidemic, regulatory and clinical experts told STAT. After all, nearly half of American adults have high blood pressure, and many people have no idea until they have a heart attack. Realistically, experts are concerned that the underlying technology is still novel and unproven, and that a flood of confusing features may mislead users about the state of their health and prevent them from pursuing necessary care.
STAT+: An ASCO preview: What to watch for at cancer research’s big meeting
This is the online version of Adam’s Biotech Scorecard, a subscriber-only newsletter. STAT+ subscribers can sign up here to get it delivered to their inbox. STAT is also producing a free pop-up newsletter about this year’s ASCO meeting. Sign up here.
Chicago, here I come. The annual meeting of the American Society of Clinical Oncology kicks off tomorrow and runs through Tuesday, June 2.
Let’s set the table for cancer research’s big event, starting with the obvious headliner: Revolution Medicines and its RAS-blocking pancreatic cancer drug daraxonrasib. Full results from the company’s Phase 3 RASolute 302 study will feature prominently at ASCO’s plenary session on Sunday afternoon. The arena-sized exhibition hall will be jam-packed.
Climate tech companies are going public. What’s next?
This year, there’s been a wave of notable energy companies going public via IPO in the US.
The solar and battery company Solv Energy went public in February, to the tune of $6 billion. X-energy, which is building small modular nuclear reactors, did the same in April, and its stocks surged on its first day of trading to hit a $11.5 billion market cap. Most recently, the geothermal company Fervo Energy went public in mid-May, and its market cap is now about $12.4 billion.
Those are all success stories in the IPO world. And it certainly doesn’t feel like a coincidence that all these companies are racing to provide electricity in an era of rising demand (partly due to data centers). Let’s take a look at how these firms are doing, what this moment says about the grid, and what’s coming next.
Let’s start with Fervo Energy, a company we’ve covered a lot over the years that’s working to develop enhanced geothermal energy. (We included it on our 2025 list of Climate Tech Companies to Watch.) While conventional geothermal requires finding specific spots with hot rock, water, and fractures to support a power plant, Fervo essentially uses fracking techniques to create the necessary conditions.
The company was founded in 2017, and it raised about $1.5 billion from investors over the years before its IPO.
Fervo’s first commercial project, Cape Station in Utah, is expected to have a capacity of about 500 megawatts. The first unit is set to start generating power for customers by October and the next two units by January 2027.
The new funding from the IPO could help the company scale. Fervo currently has over 600 megawatts’ worth of binding power purchase agreements. And it has leases for land that could together generate more than 40 gigawatts of electricity. (As of 2024, the entire US geothermal fleet had a capacity of just 4 gigawatts.)
The company also has an eye on cutting construction and drilling costs—its Cape Station plant is expected to cost about $7 per kilowatt, which is cheaper than new nuclear power plants but over twice the expense of building a new natural-gas plant in the US.
X-energy also aims to provide reliable clean power: it’s part of the wave of next-generation nuclear companies working on small modular reactors. The company is building high-temperature gas-cooled reactors, which flow helium over self-contained pebbles of nuclear fuel. These reactors will each generate 80 megawatts of electricity, less than one-tenth the output of larger ones like Unit 4 at Plant Vogtle in Georgia, the most recent addition to the commercial nuclear fleet in the US.
X-energy also saw its IPO go well, and prices surged in trading after the initial offering. One interesting tidbit here—the company had previously planned to go public in 2023 but decided against it because of difficult market conditions.
The company is still years away from demonstrating its technology in a commercial project.
You may recall a story I wrote last year about its effort to build nuclear reactors at the site of a Dow Chemical plant in Texas. The company recently received a key environmental approval for that project, though it’s still waiting for the final green light from the Nuclear Regulatory Commission to start construction.
Finally, Solv Energy builds solar and energy storage projects, mostly for utilities and independent power producers. Solar and batteries are some of the cheapest and easiest technologies to add to the grid, so this one could get a lot of capacity online, quickly. The company already has 21 gigawatts’ worth of projects operational across 35 states.
Many companies in the energy sector are pinning their hopes on the rapid growth in data center construction and operation. The AI boom has transformed the energy landscape, pushing electricity demand higher in a country where it’s been relatively flat for the last decade or so. Solv Energy mentioned data centers over a dozen times in documents filed with the Securities and Exchange Commission before its IPO.
And Fervo and X-energy are particularly connected to the tech giants driving AI. Google has been a longtime investor in Fervo and also pioneered what it calls its clean transition tariff with the company. Amazon is a client of X-energy as well as an investor; it reportedly owns close to 20% of the company.
Fervo and X-energy are also in industries that occupy a political sweet spot. President Trump and his administration have gone after wind power and other renewables, cutting off existing support and slowing approvals for new projects. Meanwhile, geothermal and particularly nuclear power have kept favor with the federal government and enjoyed continued tax credits and grant funding.
If a few big leaders cash through these IPOs, it could help investors feel more confident about supporting the energy sector, even if that money is concentrated in later-stage ventures like these rather than earlier-stage companies.
We could see other firms, particularly in nuclear and geothermal, attempt a similar route in the year ahead.
A key thing to watch here will be whether Fervo and X-energy in particular can succeed in scaling up and deploying their technology. If either of these companies stumbles or misses a timeline, it could have ripple effects for those hoping to follow in these very lucrative footsteps.
This article is from The Spark, MIT Technology Review’s weekly climate newsletter. To receive it in your inbox every Wednesday, sign up here.
The AI Hype Index: AI gets booed in graduation season
It is one thing to say AI will change the world. It is another to expect the class of 2026 to applaud it. In fact, when former Google CEO Eric Schmidt told University of Arizona graduates that their task is to help shape AI, he was met with a resounding chorus of boos. “I can hear you,” he said, before conceding that fears about disappearing jobs and a broken future were “rational.”
This is not exactly the message one hopes to hear while sweating under a polyester gown and tallying student loan payments. Graduates have been jeering at AI pep talks at other commencements too, including ceremonies at the University of Central Florida and Middle Tennessee State University. Still, increasingly loud skepticism hasn’t stopped OpenAI from winning court cases, raising enormous sums of money, and launching new partnerships. And AI is even earning some unlikely cheerleaders: Reese Witherspoon has warned women to embrace it or be replaced by it.
PRINCE: A Small-Molecule Switch for Safer Gene Editing
Although gene editing has enormous clinical promise, it still faces many obstacles that must be overcome before broad translation. For example, the genome editing field is continuously working to increase the safety of the technique. One way to do that is to control the duration of gene editing activity. However, achieving precise temporal control over these platforms is challenging.
Scientists currently lack tools that can precisely control the duration of gene editing therapies, to halt their effects after a few months or years. Researchers have developed several potential solutions, including degradable protein- or RNA-based systems, but existing approaches face limitations such as only being applicable in the liver.
Now, a new gene editing system, named PRINCE, with inducible nuclease proteins and guide RNAs, enables researchers to control the duration and specificity of gene therapies precisely with small molecules—potentially addressing a longstanding safety concern in the field.
This work is published in Science Translational Medicine in the paper, “Coordinated regulation using small-molecule drugs enables controlled therapeutic genome editing and enhanced genomic precision in situ.“
In the PRINCE CRISPR-Cas gene editing system, expression of the nuclease and the guide RNA is separately inducible by two approved small molecule drugs, enabling both temporal control and reduced off-target editing.
The platform was stable for as long as two years after genomic integration in cultured human cells. In addition, a smaller system, called Little Prince, showed promising signs of efficacy in humanized mouse models of elevated cholesterol levels and age-related macular degeneration. Little Prince uses compact nucleases that can be delivered in a single adeno-associated viral vector (AAV) for delivery.
In two mouse models, Little Prince reduced excessive cholesterol levels in mice with genetic hypercholesterolemia and showed signs of reducing lesion size in rodents with laser-induced choroidal neovascularization—a model of age-related macular degeneration.
More specifically, Little Prince “ameliorated pathological phenotypes of hypercholesterolemia (average reductions of 45% and 47% in serum total cholesterol and low-density lipoprotein cholesterol, respectively) and neovascular age-related macular degeneration, with significantly reduced lesion size and leakage (P < 0.0001).”
The system produced fewer off-target edits and lower off-target editing frequencies than constitutive nuclease expression, highlighting the utility of precise temporal control.
“PRINCE and Little Prince also provide […] capabilities that might also be useful for research objectives that include lineage tracing and conditional genetic engineering work,” the authors noted. These results, they asserted, position PRINCE and Little Prince as controlled genome editing platforms with potential for in vivo, particularly in situ, therapeutic applications.
The post PRINCE: A Small-Molecule Switch for Safer Gene Editing appeared first on GEN – Genetic Engineering and Biotechnology News.