Personalized Therapy Could Overcome Resistance in Metastatic Melanoma

Researchers at the University of Texas MD Anderson Cancer Center have identified a strategy to reverse resistance to standard treatment in BRAF-mutant advanced melanoma. Their findings, published today in Nature Communications, support using a biomarker-guided approach to improve outcomes for patients with treatment-resistant melanoma. 

“Patients whose melanoma has stopped responding to standard therapies currently have very few effective treatment options,” said  Vashisht Gopal Yennu Nanda, PhD, associate professor of melanoma medical oncology and translational molecular pathology at UT MD Anderson. “Our findings could help address this critical need for these patients by guiding clinicians toward combinations tailored to each individual’s tumors.” 

About 50% of melanoma tumors carry BRAF mutations that drive uncontrolled tumor growth. Although the standard of care, consisting of a combination of BRAF and MEK inhibitors, is initially effective in most patients, about 80% will develop resistance within two years. In many cancers, but especially in melanoma, acquired resistance is often driven by the tumor increasing production of proteins from the BCL2 family, which block apoptosis and support the survival of cancer cells. 

Yennu Nanda and colleagues tested the effects of adding a BCL2 inhibitor drug to the standard two-drug regimen in patient-derived xenograft models, which were established using melanoma tumors that had acquired resistance to standard therapy. Results showed that tumors that expressed high levels of BCL2 responded well to the triple combination, reversing resistance and inducing a complete tumor regression. 

However, tumors that expressed high levels of MCL1—another protein from the BCL2 family—did not respond to this combination. In these tumors, the researchers tested an alternative treatment course adding an experimental MCL1 inhibitor to standard treatment, which successfully led to complete tumor regression. 

“Targeted therapy works by shutting down the main signal driving melanoma growth, but tumors often have backup systems that keep them alive,” said Yennu Nanda. “By identifying which protein a tumor relies on for survival, we may be able to match patients to drug combinations tailored to their specific tumor biology.” 

MCL1 inhibitors have previously shown promising antitumor activity, but early clinical trials flagged concerning heart-related side effects that have prevented them from moving through clinical development and receiving approval. In this study, however, the combination of an MCL1 inhibitor with standard BRAF-MEK inhibitors seemed to protect cardiac cells from the harmful effects associated with these experimental drugs. 

“We did not anticipate that pairing these drugs would reduce MCL1 inhibitor toxicity,” said Michael A. Davies, MD, PhD, chair of melanoma medical oncology at UT MD Anderson. “If this finding is confirmed in clinical trials, it could give a second life to a class of drugs that has struggled to advance through development. It also reinforces that the most effective combinations are those that eliminate cancer while sparing healthy tissue.” 

Building on these findings, the researchers are now working on analyzing tumor samples from a recent Phase II clinical trial in melanoma patients who received standard treatment and a BCL2 inhibitor, with the goal of studying whether MCL1 expression can predict clinical response. Down the line, their goal is to design clinical trials where melanoma patients are matched with drug combinations based on the expression of BCL2 or MCL1 biomarkers. 

 

The post Personalized Therapy Could Overcome Resistance in Metastatic Melanoma appeared first on Inside Precision Medicine.

Affective Computing in Serious Games for Physical Rehabilitation: Scoping Review

Background: Serious games have become an alternative support for traditional physical therapy. However, many of these games do not address the emotional needs of patients. People with disabilities often experience emotions such as sadness, frustration, and even anger, which can create a barrier to their rehabilitation treatment. Objective: This review presents a comprehensive overview of technologies, techniques, and methods in affective computing as applied to serious games for physical rehabilitation and identifies key gaps to guide future research in this field. Methods: A scoping review was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, using the databases PubMed, ScienceDirect, IEEE Xplore, ACM Digital Library, PEDro, Springer, and Google Scholar. Results: The initial search yielded 5293 records, of which 9 papers met the inclusion criteria. Data were systematically extracted from these papers based on predefined research questions. Notably, engagement, tiredness, and pain were the most identified emotions, reported in 4 of 9 (50%) studies. Only 3 studies applied theoretical frameworks for emotion classification. Facial expression analysis and gesture recognition were the most frequently used affective computing techniques, yet only 2 studies implemented adaptive gameplay based on affective feedback. Conclusions: The integration of affective computing into serious games represents a promising approach for detecting affective states in patients undergoing rehabilitation. However, the limited number of primary studies, methodological limitations, and potential selection and reference-standard biases limit the reliability and generalizability of the current findings. Future research should prioritize rigorous multicenter designs, standardized evaluation protocols, and multidisciplinary collaboration. Developing these areas is essential to establishing clinical effectiveness.
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Prediction of Clinically Significant Depressive Symptoms at 2-Year Follow-Up in Older Adults: Machine Learning Study Using the English Longitudinal Study of Ageing

Background: Depression in older adults is often underdiagnosed due to atypical symptom presentation and generational stigma, leading to delayed intervention. Early identification of individuals at risk of developing elevated depressive symptoms is therefore critical, but traditional approaches show limited predictive accuracy. To date, no study has applied machine learning (ML) models to predict clinically significant depressive symptoms at 2-year follow-up in older adults in the United Kingdom using data from the English Longitudinal Study of Ageing (ELSA). Moreover, the impact of encoding strategies for categorical health care variables has not been examined. Objective: This study aimed to develop and evaluate ML models to predict the clinically significant depressive symptoms at 2-year follow-up in older adults using ELSA data. We further compared ordinal and one-hot encoding strategies across different ML architectures and identified key predictors of depressive symptoms at follow-up. Methods: Data were drawn from 4 consecutive waves of ELSA, including participants aged ≥50 years without significant depressive symptoms at the baseline wave (waves 6‐9). Clinically significant depressive symptoms were defined as 8-item Center for Epidemiologic Studies Depression Scale (CES-D 8) scores of ≥4 at the subsequent wave (waves 7‐10). Over 120 features spanning sociodemographic, psychological, and health-related domains were analyzed. Eight ML models were applied, including tree-based ensembles, deep learning architectures for tabular data, distance-based methods, probabilistic methods, and linear methods. Model performance was assessed using the area under the receiver operating characteristic curve (AUROC) and -score. Model interpretability was examined using Shapley additive explanations (SHAP). Sensitivity analyses assessed the robustness of results across alternative CES-D 8 thresholds (≥3, ≥4, and ≥5) and encoding strategies. Results: Across waves, the best-performing models achieved mean AUROC scores of 0.72‐0.73, with a peak of 0.75 in the highest-performing wave. Ordinal encoding consistently outperformed one-hot encoding across all ML models, yielding improvements in AUROCs and -scores, with the greatest increase in tree-based methods. SHAP consistently identified loneliness, sleep disturbances, and low social engagement as strong predictors of elevated depressive symptoms at follow-up. Sensitivity analyses across CES-D 8 thresholds demonstrated robust feature importance, with AUROCs ranging from 0.67 to 0.82. Traditional ML models (random forest, extreme gradient boosting, and support vector machines) generally achieved higher performance than the deep learning models for this task. Conclusions: Our findings demonstrate the feasibility of predicting clinically significant depressive symptoms at 2-year follow-up in UK older adults, with moderate accuracy. Ordinal encoding demonstrates superior performance for health care datasets with inherently ordered categorical features. The identification of consistent risk factors highlights opportunities for developing targeted clinical screening tools and preventive interventions. This study provides new evidence on depressive symptom prediction in the UK context, leveraging longitudinal data from ELSA, and contributes to advancing digital mental health research for aging populations.
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<![CDATA[Psychiatrists debunk 10 common antidepressant myths—placebo claims, addiction fears, suicide risk, overuse, and withdrawal—offering evidence-based guidance.]]>
<![CDATA[In the first ever episode of “On Your Mind With Erin Crown,” explore how tribalism hurts the field of psychiatry and ultimately patient outcomes. ]]>

Teaching AI to run with the turbines

Artificial intelligence may have captured the public imagination through chatbots and image generators, but some of its most consequential use cases are unfolding far from consumer-facing tools. In industries where physical infrastructure, operational continuity, and safety are paramount, AI is becoming a core operating layer. With its sprawling industrial systems and constant stream of operational data, the energy sector offers a glimpse into what that future could look like.

At Woodside Energy, AI adoption did not begin with generative models or enterprise copilots. The company has spent years building predictive analytics, optimization systems, and machine learning tools across exploration, drilling, maintenance, and plant operations. “We’ve always had very large volumes of operational data coming from the equipment and the plants and the assets that we operate,” says the company’s vice president for digital Andrew Melouney. “Those have created really clear, quite high-value use cases for us.”

That long-term investment in infrastructure and governance is now enabling a broader shift toward agentic AI systems that can support complex industrial workflows. Rather than replace human operators, Woodside designs AI systems to augment expertise in high-stakes environments. A prime example is its “Startup Advisor,” an AI copilot that helps operators manage the complex process of starting liquefied natural gas (LNG) plants. “We’re really thinking about, how does it support the people in the organization in terms of empowering them to make better decisions, to make faster decisions,” Melouney explains.

The company’s approach reflects a wider evolution taking place across industrial AI: graduating from isolated experiments to enterprise-wide systems built on standardized platforms, governed data, and repeatable deployment patterns. That transition, Melouney argues, requires organizations to rethink both their technology stacks and how work itself gets done. “We’re not just bolting AI onto an existing process,” he says. “We’re deeply thinking about how that work needs to be reimagined.”

Melouney’s motto has become: “Think big, prototype small, and scale fast.”

As AI systems become more autonomous and interconnected, the companies poised to succeed may be those that spent years building the operational foundations beneath the hype.

“Our ambition is really for an autonomous enterprise, where we have agents with agency that are able to really deeply interact with our core workflows,” says Melouney.

This episode of Business Lab is produced in partnership with Infosys.

Full Transcript:

Megan Tatum: From MIT Technology Review, I’m Megan Tatum, and this is Business Lab, the show that helps business leaders make sense of new technologies coming out of the lab and into the marketplace.

This episode is produced in partnership with Infosys.

Now, when people think about artificial intelligence, they often picture chatbots or productivity tools, but some of the most sophisticated and high impact uses of AI are actually happening far from consumer apps, inside complex industrial environments where safety, reliability, and physical systems matter. The global energy sector is a prime example.

Companies like Woodside Energy, a global energy producer headquartered in Western Australia, have been applying AI for more than a decade now, from advanced analytics and operations, to remote decision support, to smarter maintenance, and energy efficiency across large scale assets. Today, Woodside is scaling that experience, embedding AI more deeply across its operations and the enterprise with a strong focus on governance, data quality, and human accountability.

Two words for you: technological fuel.

My guest today is Andrew Melouney, vice president for digital at Woodside Energy. Welcome, Andrew.

Andrew Melouney: Thanks, Megan. It’s great to be here.

Megan: Lovely to have you. Now, Andrew, as I said there, the energy sector has approached AI quite differently from technology or consumer businesses. Early value has emerged in operational and industrial environments, rather than consumer-facing generative AI tools. Why is that? And what differentiates the energy sector’s AI journey?

Andrew: Megan, I think it really comes down to the nature of the work we do. Energy operations and what Woodside does is very asset intensive, it’s very safety critical, and it’s highly physical. And when you think about how Woodside operates, we operate across the full value chain. We do exploration through to drilling and subsurface work, to project development, all the way through to operating assets, which are often operated in harsh and remote locations, and then global energy portfolio marketing and trading as well.

We’ve always had very large volumes of operational data coming from the equipment and the plants and the assets that we operate, and those have created really clear, quite high-value use cases for us. When you think about reliability, when you think about safety and efficiency, those are really critical things for a company like Woodside. We’ve been doing traditional AI for many years now. If you think about analytics, if you think about optimization, if you think about things like predictive models, those techniques we’ve been applying to our data sets and to our business since around 2015.

And more recently with the advent of generative AI, we’ve really found that we’ve got a pretty strong and awesome foundation to build on top of and to really solve problems in the service of improving the business. And again, whether that is keeping people safe, keeping the environments we operate in safe, or improving returns for the organization.

Megan: Fantastic. I mean you touched on it there, but how has this reality shaped your own AI strategy at Woodside? Where did you start, and where did the technology prove most impactful in those early days?

Andrew: Well, like I said, we’ve had a very long journey, in terms of understanding our operational data, recognizing the value of it, and collecting it at scale so that we can use it. And we’ve been very deliberate in that approach, Megan. We’ve really thought about where the value is and where the risks were manageable. And we’ve started looking at, in today’s world from an agentic AI perspective, we’ve started looking at the problems that were solved with traditional AI and machine learning and data science in the past. And we’ve started to think about, where can we then layer agentic AI over the top to provide an even better outcome?

For our asset intensive industry and organization, we’re looking at areas such as maintenance optimization. We’re looking at areas such as, how do we ensure our LNG plants start up reliably, consistently, and safely? And we’re considering really our frontline workforce and making sure that we’re giving people on the frontline the tools required to do their jobs. When we think about AI, we’re really thinking about, how does it support the people in the organization in terms of empowering them to make better decisions, to make faster decisions? I think over time, this has just evolved from what has been traditional analytics to now artificial intelligence and generative AI. And we’ve learned along the way that the technology is important, but it’s about aligning people, processes, and the technology together.

We’ve spent a long time not only in collecting the data and having a well-curated data set that we can build on top of, but we’ve also spent a lot of time teaching people how to work in agile ways, how to do design thinking, how to problem solve, and how to really make sure that the technology that, say, my team can bring to bear to the organization is adopted effectively and purposefully. And I think once we had that solid foundation in place from a technology perspective, from a data perspective, once we got strong trust built between our digital teams and the organization, we really saw quite a material uptick and the scaling of technology occur more broadly across the enterprise.

Megan: Fantastic. That people piece so important, isn’t it? It’s just a tool, technology, that needs to be in the right hands. And you touched on data there; industrial AI obviously depends on vast amounts of data. Can you walk us through how you’ve approached data at Woodside in a little more detail? How it’s structured and governed, and how tools like maintenance intelligence as well fit into that.

Andrew: Well, data is really foundational and fundamental to everything we do, particularly from a technology perspective. It gives us the ability to innovate at pace when we are building over the top of a strong foundation. As I said before, we’ve had the benefit of a long-term investment in our underlying operational data. I think the way we think about data is that it’s an asset for us.

And when you think about operating a facility where you’ve got sensors everywhere, you’ve got data streaming in real time, you’ve got operators needing to make decisions in real time, we have consciously made a decision over many, many years to invest in that enterprise scale data platform to make sure that it’s secure. We’ve got well-structured data assets, and we’ve got strong governance over the top of that data so that when it is used, when it’s built in a data science application or an AI agent, that we’ve got a level of trust in it that it’s going to be used responsibly. And that when it’s used, it can be trusted to give the outcome that we expect.

We have developed platforms that continuously ingest really high frequency data from the assets and from our enterprise systems. Once we’ve been able to develop solutions on top of that, parts of the business that might own the systems that collect that data, they see the value in it.

When you look at something like maintenance intelligence is a really good example of how we’ve been able to take something that we’ve been working on for a long time. Woodside does a lot of maintenance, it’s a very important part of our business, and it occurs across all of our operating assets. But we have been looking at how we do predictive analytics and predictive maintenance for a long time across that data set that we own. And something like maintenance intelligence is a solution that gives us the ability to optimize how we do that maintenance. And what it does is it analyzes historical maintenance records, alongside the performance of the equipment. And again, by having that data set well-governed and in one place, we get the ability to correlate different data sets, such as maintenance records out of SAP, alongside say equipment and performance coming from our time series data lake.

And when we build over the top of that, something like maintenance intelligence gives us the opportunity to recommend to the assets what the optimal timing for maintenance activities might be, and really give what is quite a simple aim, which is do the right work at the right time. And with something like maintenance intelligence, we have seen the opportunity, and we have the opportunity to reduce maintenance hours by up to 15% over five years on one of the assets that we’ve piloted this on. And as we’ve built out that underlying analytical model, we’re now able to put agentic AI over the top of that and provide better insights and optimize that solution more.

It really comes down to providing our asset teams and our operational teams with the right decision support capability that ensures they’re still accountable to make the decision and to ensure the right work is being done, but we are giving them the best possible opportunity to use their judgment and experience with the data that we provide to make the right decision.

Megan: Sounds like a really impactful change. Last year also marked a milestone in moving from early AI learnings to scale, using AI more deliberately as a force multiplier. What transition were you trying to make and how did you approach it?

Andrew: Well, Megan, we’ve had a philosophy for a long time in Woodside from an innovation perspective, where we really want to think big, we want to prototype small, and we want to scale fast. We want to find big opportunities that we can go after, but we want to ensure that we look at how we deploy those on a small scale first, and then provide the right learning and insight that then can scale it everywhere. Something like maintenance intelligence is a good example of that, or our Startup Advisor, where we know that we’ve got multiple plants that we need to start up. We know that we’ve got multiple assets that need to do maintenance, so we have a big, bold ambition about how we can improve and optimize that. We start with a small prototype; it might be one subsystem, it might be just a part of an asset, and then we scale it out, we learn, and we scale faster.

I think from an AI learning perspective, one of the key things we’ve learned is really the transition from moving from isolated AI solutions to a more coordinated enterprise-wide capability. If you look back maybe 18 months, two years, in our generative AI journey, we rarely started by deploying AI as broadly as we could in the organization from a personal productivity perspective. And probably being quite open in terms of the problems that we will solve, the business problems that we’ll solve with AI. That had a lot of benefits for us in terms of allowing our organization to get to know AI, get to know the capabilities, to build the trust in it.

What we’ve learned though is that we’ve needed to pivot from that to being a little bit tighter in terms of where we are going to invest our time and resources and more higher value solutions. How do we then enable and empower the rest of the organization so that they can actually effectively problem solve with technology in their domain or in their personal productivity without having to come to a central team?

When we think about that, think big, prototype small, scale fast, has been something really important for us. The transition from a more broader approach to use case development and solution development to now a narrower focus on the high value priorities. We’ve seen that paying dividends to us and allowing us to go after solutions and opportunities, things like Startup Advisor.

And so our Startup Advisor is a agentic AI solution that really aims to optimize and empower and better support our operators that sit in front of a panel and have to start up LNG plants, which are incredibly technical facilities and require really specialist skills to start up. And so our Startup Advisor is almost like a copilot that sits alongside those operators, and it gives them the ability to be able to play back previous startups. It gives them the ability to look at how the current startup is progressing, and it provides them better insights to optimize how they start up that facility. And again, starting up an LNG facility is incredibly complex.

Megan: I can imagine.

Andrew: When we think about opportunities like Startup Advisor, again, it goes back to that think big, prototype small, and scale fast. We started with a very bold vision of, how do we start up all of our LNG plants in a much more structured and optimized fashion? How do we better support our panel operators? How do we make, say, a more junior panel operator have a copilot that can help them almost like an experienced panel operator sitting next to them? And when we think about that vision and the ability then to prototype on a small scale and then scale fast, I think it’s been really successful for us.

As we scale, we’ve just naturally expanded into more agent-based solutions. Today, we’ve got around 50 AI agents in production, supporting both our operating assets and our enterprise workflows. These tools have been proven in live environments, and we have really seen the benefit of being able to shift from point solutions that maybe solve small scale problems in specific areas, to AI and agentic solutions with agency that can really work across our workflows.

We’re able to do this because we’ve standardized on the platform that we build on and we’ve got repeatable patterns. That’s been another really important learning for us, is that we don’t want to build 50 solutions in 50 different ways. We really want to be empowering our organization and our technical teams and the users of our solutions to roll them out quickly, to roll them out safely, and to do it in a patternized and platform manner.

But the last point I’ll make, Megan, from a learning perspective is that we’ve really understood that a strong governance around how AI is deployed and developed is critical for us, and it’s critical for us to go fast as well. The traditional ways of governing how we roll out different solutions or digital systems isn’t going to scale to the breadth that we need when we are thinking about AI. Being able to have a clear philosophy around how we innovate, transitioning from isolated solutions to that enterprise-wide capability, and making sure that we’ve got strong platforms with strong patterns and clear governance are the three really critical things that we’ve learned.

Megan: Such important pillars, all of them. And you’ve been working with Infosys on this journey. How has that partnership helped accelerate scaling and embedding AI across the business?

Andrew: Well, Infosys is our managed service provider, and so they play a really critical role in the operations of our core business. One of the things that I like to say is that our license to innovate is based on our license to operate. And so, for my team to be able to turn up to an operating asset or a corporate function and have the trust that’s needed to be able to innovate and reimagine and redesign how work gets done, to be able to do that, we need to make sure that our core platforms, our core systems, our applications are running really reliably, safely, and consistently every day. Having an experienced partner like Infosys looking after those core operations in partnership with our internal teams is really, really important to us.

As we move from pilots to enterprise-wide deployment, the ability to partner with someone like Infosys also gives us the ability to scale. And so being from Perth and Western Australia, while we’ve got a really strong local team in Western Australia, and we’ve also got a very strong team in some of our other operating locations, like everyone, we’re struggling to find people that can fill AI roles. Being able to partner with Infosys and have a number of different operating models at our disposal becomes really important for us. Having co-mingled teams where they are staff, they are Infosys staff, Woodside staff, and some of our other partners, really just brings diversity of thought and experience to how we solve problems.

Fundamentally, the partnership has allowed us to operate and innovate with more confidence. While Woodside always retains ownership of the strategy and where we’re going and the governance and my teams remain accountable for the outcomes, we can’t do what we do without strong partnerships like the one we have with Infosys.

Megan: Fantastic. And as AI adoption scales, you mentioned yourself, governance becomes increasingly important. How challenging has that been, and what guardrails have you put in place at Woodside?

Andrew: So, Megan, governance is really important to us, and we operate in a well-regulated environment. That means we’ve got to make really deliberate and well-reasoned decisions when we’re thinking about how we deploy technology into our organization, whether it’s artificial intelligence or anything else, for that matter. And so, governance is really central to how we approach the execution of our AI strategy at Woodside.

We’ve got maybe two or three really key things that we’ve put in place. The first one is just making sure that every AI use case goes through a structured assessment, and that’s making sure it meets our privacy controls, our cyber controls. We’re also asking the question, not just, could we do this, but should we do this? We’ve really got to bring together safety, ethics, transparency, accountability, and make sure that we make an informed decision. When an AI solution is going through that structured assessment, if there are concerns about how we might use that solution, it then goes to an AI council that’s made up of senior leaders across the organization. That council and that group really oversee some of the prioritization and risk management. That’s where we can have really strong, robust debates around, again, could we do something, should we do it, and how do we mitigate any of the risks that we might introduce here?

I think the last one, Megan, is really around lifecycle management. When you start thinking about, we’ve got 50 at the moment, but if we had 500 agents working in our organization, really amplifying the experience and the decision-making and the value creation of our staff, we really want to have an ability to manage the lifecycle of how those agents operate. We want to know, how many people are using them? What’s the efficacy and the outcome? Is there model drift? Do we need to retune or retrain? I think that’s an area where many organizations, including Woodside, are still leaning into and still figuring out the best way to do this. We can do it quite easily with 50 agents, but 500, 5,000, 50,000 becomes an opportunity for us. Again, thinking about how we partner with others, solving problems like that really present an opportunity to co-create and to co-solve with some of our partners, like with Infosys.

Megan: Fantastic. Just to close, what’s your long-term vision for AI at Woodside? How do you see this evolving over the years ahead, and what could it unlock for the sector in your view?

Andrew: So Megan, I think our ambition is really for an autonomous enterprise, where we have agents with agency that are able to really deeply interact with our core workflows. The outcome that we want to get from that is to protect our people, to protect the environments we operate in, and to be able to provide energy at a lower cost to the world. When we think about that ambition, we can really see that being applied to almost all of the areas that Woodside work in. Whether that’s from exploration through to project developments, through to operations or marketing, the scale of the opportunity in front of us and the ability for us to really change the way that work flows through the organization is really exciting.

For us, there’s three things that we have to get right in terms of being able to execute on that ambition. The first one is really thinking about how the work gets done in the organization so that we’re not just bolting AI onto an existing process, but we’re deeply thinking about how that work needs to be reimagined. We’ve also got to think about how we enable our workforce to work differently. Providing them with the skills and the tools and the ability to really harness the power of the technology that we provide.

Secondly, we’ve got to continue to move from and restrain ourselves from deploying point solutions that solve very narrow problems, to having more connected, agentic systems of systems that can interact with each other. To do that, and if we do that successfully, that’s where we really get the high value unlock from agents being able to interact with workflows and really change how the work gets done.

And lastly, Megan, it’s about how we must continue our philosophy of thinking big, prototyping small, and scaling fast.

Megan: Which is a fantastic lens to which to make all these decisions. Thank you so much, Andrew. That was Andrew Melouney, vice president for digital at Woodside Energy, whom I spoke with from Brighton in England.

That’s it for this episode of Business Lab. I’m your host, Megan Tatum. I’m a contributing editor and host for Insights, the custom publishing division of MIT Technology Review. We were founded in 1899 at the Massachusetts Institute of Technology, and you can find us in print, on the web, and at events each year around the world. For more information about us and the show, please check out our website at technologyreview.com.

This show is available wherever you get your podcasts. And if you enjoyed this episode, we hope you’ll take a moment to rate and review us. Business Lab is a production of MIT Technology Review, and this episode was produced by Giro Studios. Thanks ever so much for listening. Goodbye.

This content was produced by Insights, the custom content arm of MIT Technology Review. It was not written by MIT Technology Review’s editorial staff. It was researched, designed, and written by human writers, editors, analysts, and illustrators. This includes the writing of surveys and collection of data for surveys. AI tools that may have been used were limited to secondary production processes that passed thorough human review.

The Download: a startup has a solution for AI’s groupthink problem

This is today’s edition of The Download, our weekday newsletter that provides a daily dose of what’s going on in the world of technology.

LLMs are stuck in a groupthink groove. This startup is trying to get them out.

Open up your chatbot of choice—Claude, ChatGPT, Gemini—and type “Give me a random number between 1 and 10.” You’re going to get 7. Almost always. 

That won’t work every time—but if it did for you, you may wonder if I have superpowers. I don’t.

The truth is that most large language models are stuck in a rut. They are far more predictable and far less creative in their responses than you might expect. That’s fine for tasks like coding or research, but groupthink is a problem when you’re brainstorming or planning your next vacation.

The Australian startup Springboards has a solution. It built an LLM called Flint, which has been trained to come up with a wider variety of responses than mainstream LLMs to open-ended questions such as “Where should I go in Europe?”

Meet the company pushing chatbots away from the obvious.

—Will Douglas Heaven

The must-reads

I’ve combed the internet to find you today’s most fun/important/scary/fascinating stories about technology.

1 Scientists say they have built a cell from scratch for the first time
Built with lab-made DNA, it can feed, grow, and multiply. (CNN)
+ It brings us closer to creating synthetic life. (Quanta)
+ And is arguably the greatest feat of bioengineering yet. (New Scientist $)
+ But also raises concerns over the dangers of synthetic biology. (NYT $)
+ Mirror organisms could threaten life on Earth. (MIT Technology Review)

2 OpenAI has proposed giving the Trump administration a 5% stake
Talks over a public ownership deal come amid rising political pressure.(FT $)
+ OpenAI also proposed other US AI giants providing a 5% stake. (CNBC)
+ That could include Anthropic, Google, and Meta. (Bloomberg $)
+ President Trump says he wants the public to have a stake in AI. (BBC)

3 Singapore has seized a $42 million mansion tied to Nvidia chip smuggling
It was seized as part of an investigation into alleged illegal trading. (BBC)
+ Days earlier, Supermicro’s Taiwan offices were raided in the probe. (FT $)

4 Anthropic’s Fable 5 is back online
But queries posing security risks may be routed to less powerful models. (Axios)
+ Anthropic restored access yesterday after the US lifted an export ban. (BBC)
+ But the battle over how to tame AI has just begun. (WSJ $)
+ Anthropic has launched a new AI science product. (MIT Technology Review)

5 Meta is building its own cloud infrastructure business
It’s exploring two ways of monetizing AI compute and models. (Bloomberg $)
+ One is selling access to models hosted on Meta’s infrastructure. (CNBC)
+ The other is selling “raw” computing power. (TechCrunch)

6 PlayStation will stop releasing games on discs in 2028
Future PS5 games will be digital-only releases. (Verge)
+ The news comes days after reports that GTA VI will have no disc. (BBC)
+ It’s put a nail in physical media’s coffin. (Wired $)

7 A low-cost Chinese AI model is catching up with US giants on their home turf
Western customers are drawn to GLM-5.2’s cheap but powerful model. (Reuters $)
+ Chinese open-source models are spreading fast. (MIT Technology Review)

8 Google has lost its fight against a record €4.1 billion EU antitrust fine
It was charged in 2018 for using Android to ‌block rivals. (CNBC)

9 The UN has launched an “AI for Good” commission
Salesforce CEO Benioff and Rwandan President Kagame will co-chair it. (Axios)

10 People prefer AI impersonators over politicians
The study’s findings raise alarm bells around potential public deception. (404 Media)

Quote of the day

“If AI overdelivers, it will impact financial stability. If AI underdelivers, it will impact financial stability.”

—Torsten Slok from Apollo Global Management shares common concerns about AI at the European Central Bank’s annual conference, Reuters reports.

One More Thing


America was winning the race to find Martian life. Then China jumped in.

In July 2024, after more than three years on Mars, the Perseverance rover came across a peculiar rocky outcrop. Instead of the usual crystals or sedimentary layers, this one had spots. Those specks were the best hint yet of alien life.  

NASA began a new mission to bring the rocks back to Earth to study. But now, just over a year and a half later, the project is on life support. As a result, those oh-so-promising rocks may be stuck out there forever. 

This also means that, in the race to find evidence of alien life, America has effectively ceded its pole position to its greatest geopolitical rival: China. Beijing is now moving full steam ahead with its own version of NASA’s mission. 

Here’s how the search for Martian life has become a contest between two superpowers.

—Robin George Andrews

We can still have nice things

A place for comfort, fun, and distraction to brighten up your day. (Got any ideas? Drop me a line.)

+ The classic arcade game Crazy Taxi is returning.
+ Thom Yorke’s live set from the Sydney Opera House is a reminder of what an extraordinary performer he is.
+ Peer into 1,000 gloriously illuminated New York apartment windows at night in this generative photography project.
+ The Orion constellation dazzlingly displays every stage of star formation in this image from the James Webb Space Telescope.

Top image credit: Sarah Rogers/MITTR | Photos Getty

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You can follow me on LinkedIn. Thanks for reading!

—Thomas

EFE-8c4, a polyamine from Elaeagnus multiflora, protects neuronal cells by regulating oxidative stress and apoptotic pathways

Neurological disorders, including depression, cognitive impairment, and neurodegenerative diseases, are closely associated with oxidative stress, apoptotic neuronal loss, and impaired neuronal differentiation. Polyamine derivatives from natural products have emerged as potential neuroprotective agents, although their mechanisms remain incompletely understood. In this study, three polyamine compounds isolated from Elaeagnus multiflora fruit were evaluated in SH-SY5Y cell models of oxidative and glucocorticoid-induced stress. Among these, EFE-8c4 exhibited the most pronounced neuroprotective activity, significantly restoring cell viability under corticosterone-induced stress and attenuating oxidative damage induced by hydrogen peroxide. Mechanistically, EFE-8c4 modulated apoptotic signaling by increasing Bcl-2 expression while suppressing Bax, caspase-8, and p53 activation, thereby restoring the balance between pro- and anti-apoptotic pathways. In addition, EFE-8c4 reduced intracellular reactive oxygen species accumulation and enhanced the expression of PCNA and βIII-tubulin, indicating improved cell survival capacity and neuronal phenotype maintenance. Furthermore, EFE-8c4 partially reduced apoptotic cell populations under corticosterone exposure. Collectively, these findings demonstrate that EFE-8c4 exerts multi-target neuroprotective effects through coordinated regulation of apoptosis, oxidative stress, and neuronal differentiation-related pathways, highlighting its potential as a candidate for the treatment of oxidative stress-associated neurological disorders.

Modulating autonomic nervous system activity with transcutaneous auricular vagus nerve stimulation in Parkinson’s disease: a proof of concept study

BackgroundCardiovascular dysautonomia is a debilitating non-motor symptom of Parkinson’s disease (PD) that limits exercise capacity and neurorehabilitation outcomes. Transcutaneous auricular vagus nerve stimulation (taVNS) is an emerging non-invasive neuromodulatory therapy that modulates cardiovascular activity and could potentially serve as an adjunct to exercise, yet its physiological effects on cardiovascular function in PD remains unexplored.ObjectiveThis proof-of-concept, sham-controlled crossover pilot study (N = 8) investigated the acute effects of taVNS on cardiovascular autonomic activity in idiopathic PD.MethodsParticipants underwent active taVNS (30 Hz, 250 μs, 0.1–4 mA) or sham stimulation (0 mA) during a 15-min resting phase, immediately followed by the Ewing Battery of cardiovascular reflexes. Acute autonomic shifts were phenotyped using continuous heart rate variability (HRV) monitoring.ResultsThis proof-of-concept protocol was feasible, as all participants completed the randomized crossover stimulation visits and autonomic reflex testing without adverse events. Baseline autonomic burden (COMPASS-31) was associated with the magnitude of heart rate response to active stimulation. Immediately following stimulation and during the deep breathing challenge, active taVNS was associated with directionally consistent changes in vagally mediated HRV metrics including RMSSD, pNN50, and HF power, relative to sham.ConclusionContinuous HRV monitoring and autonomic reflex testing appears feasible for characterizing acute autonomic responses to taVNS in PD. Active stimulation was associated with directional changes in vagally mediated HRV metrics during the post-stimulation period and during deep breathing, supporting the biological plausibility of acute autonomic modulation. These preliminary findings justify larger, adequately powered studies designed to determine whether taVNS can reliably modulate cardiovascular autonomic regulation and inform rehabilitation optimization in PD.