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Human interpretable grammar encodes multicellular systems biology models to democratize virtual cell laboratories

We developed a plain text modeling language—a cell behavior hypothesis grammar—to easily build virtual cell models and connect them to data, helping scientists to unlock the hidden dynamics of tissues. We provide examples showing how to use them in virtual experiments exploring how cancer responds to the cells in its environment and how the brain forms layers in development.

Circulating tumour cells & circulating tumour DNA in patients with resectable colorectal liver metastases (MIRACLE): a prospective, observational biomarker study

EClinicalMedicine. 2025 Aug 12;87:103406. doi: 10.1016/j.eclinm.2025.103406. eCollection 2025 Sep.

ABSTRACT

BACKGROUND: Recurrence risk after curative surgery for colorectal liver metastases (CRLM) remains high, underlining the need to identify prognostic markers enabling more individualised treatment approaches.

METHODS: In the MIRACLE, a prospective, observational biomarker study, a total of 188 patients with isolated, resectable CRLM without (neo)adjuvant chemotherapy were included between October 2015 and December 2021. Blood samples were collected before surgery (baseline) and three weeks after surgery. The primary objective was to assess the potential association between postoperative circulating tumour DNA (ctDNA) detection and recurrence of disease for patients with resectable CRLM within one year after resection. The secondary objective was the association between recurrence of disease within one year and detection of circulating tumour cells (CTCs). Baseline ctDNA was measured by next generation sequencing using a targeted panel (Oncomine Colon cell-free DNA assay) and postoperatively by digital PCR on genetic variants found preoperatively with the Oncomine panel. CTCs were enumerated using the FDA-approved CellSearch system.

FINDINGS: ctDNA was detected in 117/187 patients (63%) at baseline, and 28/104 evaluable patients (27%) still had detectable ctDNA postoperatively. CTC enumeration resulted in positivity for 37/183 patients (20%) at baseline and 14/158 patients (9%) postoperatively. No association was found between 1-year recurrence-free survival (RFS) and the presence of CTCs or ctDNA at baseline. In contrast, patients with postoperative undetectable ctDNA had a significantly improved 1-year RFS compared to patients with postoperative ctDNA (54% [95% CI 44%-67%] vs. 25% [95% CI 13%-47%], log-rank p = 0.0011). Similarly, patients with postoperative detectable CTCs had a significantly shorter 1-year RFS compared to patients without postoperative CTCs (15% [95% CI 4%-55%] vs. 53% [95% CI 45%-62%], log-rank p 0.0004). Also in multivariable analysis, detectable ctDNA and CTCs after surgery remained independently associated with a shorter 1-year RFS (HR 2.35; 95% CI 1.34-4.11; p = 0.0028 and HR 2.98; 95% CI 1.56-5.71; p = 0.0010, respectively).

INTERPRETATION: This is the first study conducted in patients with resectable CRLM without (neo)adjuvant chemotherapy, which demonstrates the impact of postoperative detectable circulating tumour load on 1-year RFS. Postoperative ctDNA and CTC detection both represent strong, independent predictors for a shorter RFS after local treatment, as opposed to preoperative detection.

FUNDING: This work was supported by KWF Kankerbestrijding (Dutch Cancer Society, EMCR 2014-6340).

PMID:40838198 | PMC:PMC12361997 | DOI:10.1016/j.eclinm.2025.103406

Genetic and epigenetic dysregulation of CR1 is associated with catastrophic antiphospholipid syndrome

Ann Rheum Dis. 2025 Aug 20:S0003-4967(25)04249-9. doi: 10.1016/j.ard.2025.07.016. Online ahead of print.

ABSTRACT

OBJECTIVES: Catastrophic antiphospholipid syndrome (CAPS) is a complement-driven thrombotic disorder, characterised by widespread thrombosis and multiorgan failure. We identified rare germline variants including complement receptor 1 (CR1) in 50% of patients with CAPS. Here, we define CR1 dysregulation mechanisms (genetic/epigenetic) underlying complement-mediated thrombosis in CAPS and support C5 inhibition as a potential therapy.

METHODS: We quantified CR1 expression by flow cytometry across haematopoietic cell types. CRISPR/Cas9 genome editing of TF-1 (erythroleukaemia) cells was performed to generate CR1 'knock-out' and 'knock-in' lines with patient-specific CR1 variants. Multiomics analysis was performed to investigate the role of methylation in patients with reduced CR1 expression. Functional impact of low CR1 was assessed by complement-mediated cell killing using modified Ham assay, cell-bound complement degradation products through flow cytometry, and circulatory immune complexes in serum samples through ELISA.

RESULTS: CR1 expression in erythrocytes was markedly reduced on CAPS erythrocytes (n = 9, 21.80%) compared to healthy controls (HCs; n = 35, 84.04%), with promoter hypermethylation emerging as a plausible epigenetic mechanism for CR1 downregulation. Novel germline variant (CR1-V2125L; rs202148801) mitigated CR1 expression and increased complement-mediated cell death of knock-in cell lines. Erythrocytes from the patient with the CR1-V2125L variant had low CR1 expression. Levels of circulating immune complexes, which are bound and cleared by CR1 on erythrocytes, were higher in acute CAPS (n = 3, 25.55 µg Eq/mL) than HCs (n = 3, 7.445 µg Eq/mL). Five patients were treated with C5 inhibition which mitigated thrombosis.

CONCLUSIONS: Genetic or epigenetic-mediated CR1 deficiency is a potential hallmark of CAPS and predicts response to C5 inhibition.

PMID:40841298 | DOI:10.1016/j.ard.2025.07.016

Liquid biopsy in lung cancer

Breathe (Sheff). 2025 Aug 19;21(3):250051. doi: 10.1183/20734735.0051-2025. eCollection 2025 Jul.

ABSTRACT

Lung cancer is the leading cause of cancer-related mortality worldwide, with nonsmall cell lung cancer (NSCLC) accounting for the majority of cases. Despite advancements in therapeutics, outcomes remain poor due to late-stage diagnoses and the molecular complexity of the disease. Liquid biopsy, a minimally invasive diagnostic approach, has emerged as a potentially transformative tool in lung cancer. The detection of tumour-derived biomarkers, such as circulating-tumour DNA, circulating tumour cells and exosomes, can be analysed for molecular profiling, early detection and monitoring of disease progression. There have been significant advancements of liquid biopsy technologies, such as next-generation sequencing and droplet digital PCR, that identify actionable mutations, detect resistance mechanisms and improve therapeutic outcomes. While there are still challenges like detecting early-stage disease and the risk of false positives, the combination of multi-omics data and artificial intelligence has the potential for more personalised and precise cancer treatments. Liquid biopsy represents a paradigm shift in the early detection and personalised treatment of lung cancer, offering significant potential to improve patient outcomes.

PMID:40837417 | PMC:PMC12362143 | DOI:10.1183/20734735.0051-2025

  • ✇MIT Technology Review
  • In a first, Google has released data on how much energy an AI prompt uses Casey Crownhart
    Google has just released a technical report detailing how much energy its Gemini apps use for each query. In total, the median prompt—one that falls in the middle of the range of energy demand—consumes 0.24 watt-hours of electricity, the equivalent of running a standard microwave for about one second. The company also provided average estimates for the water consumption and carbon emissions associated with a text prompt to Gemini. It’s the most transparent estimate yet from a Big Tech company
     

In a first, Google has released data on how much energy an AI prompt uses

21 August 2025 at 20:00

Google has just released a technical report detailing how much energy its Gemini apps use for each query. In total, the median prompt—one that falls in the middle of the range of energy demand—consumes 0.24 watt-hours of electricity, the equivalent of running a standard microwave for about one second. The company also provided average estimates for the water consumption and carbon emissions associated with a text prompt to Gemini.

It’s the most transparent estimate yet from a Big Tech company with a popular AI product, and the report includes detailed information about how the company calculated its final estimate. As AI has become more widely adopted, there’s been a growing effort to understand its energy use. But public efforts to directly measure the energy used by AI have been hampered by a lack of full access to the operations of a major tech company. 

Earlier this year, MIT Technology Review published a comprehensive series on AI and energy, at which time none of the major AI companies would reveal their per-prompt energy usage. Google’s new publication, at last, allows for a peek behind the curtain that researchers and analysts have long hoped for.

The study focuses on a broad look at energy demand, including the power used not only by the AI chips that run models but also by all the other infrastructure needed to support that hardware. 

“We wanted to be quite comprehensive in all the things we included,” said Jeff Dean, Google’s chief scientist, in an exclusive interview with MIT Technology Review about the new report.

That’s significant, because in this measurement, the AI chips—in this case, Google’s custom TPUs, the company’s proprietary equivalent of GPUs—account for just 58% of the total electricity demand of 0.24 watt-hours. 

Another large portion of the energy is used by equipment needed to support AI-specific hardware: The host machine’s CPU and memory account for another 25% of the total energy used. There’s also backup equipment needed in case something fails—these idle machines account for 10% of the total. The final 8% is from overhead associated with running a data center, including cooling and power conversion. 

This sort of report shows the value of industry input to energy and AI research, says Mosharaf Chowdhury, a professor at the University of Michigan and one of the heads of the ML.Energy leaderboard, which tracks energy consumption of AI models. 

Estimates like Google’s are generally something that only companies can produce, because they run at a larger scale than researchers are able to and have access to behind-the-scenes information. “I think this will be a keystone piece in the AI energy field,” says Jae-Won Chung, a PhD candidate at the University of Michigan and another leader of the ML.Energy effort. “It’s the most comprehensive analysis so far.”

Google’s figure, however, is not representative of all queries submitted to Gemini: The company handles a huge variety of requests, and this estimate is calculated from a median energy demand, one that falls in the middle of the range of possible queries.

So some Gemini prompts use much more energy than this: Dean gives the example of feeding dozens of books into Gemini and asking it to produce a detailed synopsis of their content. “That’s the kind of thing that will probably take more energy than the median prompt,” he says. Using a reasoning model could also have a higher associated energy demand because these models take more steps before producing an answer.

This report was also strictly limited to text prompts, so it doesn’t represent what’s needed to generate an image or a video. (Other analyses, including one in MIT Technology Review’s Power Hungry series earlier this year, show that these tasks can require much more energy.)

The report also finds that the total energy used to field a Gemini query has fallen dramatically over time. The median Gemini prompt used 33 times more energy in May 2024 than it did in May 2025, according to Google. The company points to advancements in its models and other software optimizations for the improvements.  

Google also estimates the greenhouse-gas emissions associated with the median prompt, which they put at 0.03 grams of carbon dioxide. To get to this number, the company multiplied the total energy used to respond to a prompt by the average emissions per unit of electricity.

Rather than using an emissions estimate based on the US grid average, or the average of the grids where Google operates, the company instead uses a market-based estimate, which takes into account electricity purchases that the company makes from clean energy projects. The company has signed agreements to buy over 22 gigawatts of power from sources including solar, wind, geothermal, and advanced nuclear projects since 2010. Because of those purchases, Google’s emissions per unit of electricity on paper are roughly one-third of those on the average grid where it operates.

AI data centers also consume water for cooling, and Google estimates that each prompt consumes 0.26 milliliters of water, or about five drops. 

The goal of this work was to provide users a window into the energy use of their interactions with AI, Dean says. 

“People are using [AI tools] for all kinds of things, and they shouldn’t have major concerns about the energy usage or the water usage of Gemini models, because in our actual measurements, what we were able to show was that it’s actually equivalent to things you do without even thinking about it on a daily basis,” he says, “like watching a few seconds of TV or consuming five drops of water.”

The publication greatly expands what’s known about AI’s resource usage. It follows recent increasing pressure on companies to release more information about the energy toll of the technology. “I’m really happy that they put this out,” says Sasha Luccioni, an AI and climate researcher at Hugging Face. “People want to know what the cost is.”

This estimate and the supporting report contain more public information than has been available before, and it’s helpful to get more information about AI use in real life, at scale, by a major company, Luccioni adds. However, there are still details that the company isn’t sharing in this report. One major question mark is the total number of queries that Gemini gets each day, which would allow estimates of the AI tool’s total energy demand. 

And ultimately, it’s still the company deciding what details to share, and when and how. “We’ve been trying to push for a standardized AI energy score,” Luccioni says, a standard for AI similar to the Energy Star rating for appliances. “This is not a replacement or proxy for standardized comparisons.”

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