CTHULHU STUDIES

3D structure of DNA may explain how cephalopods evolved complex brains

Study suggests that the 3D "entanglement" of DNA may help drive evolutionary innovation

University of Vienna

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Californian two-spot octopus (Octopus bimaculoides). Embryo at the final stage before hatching. The species is named after the two prominent blue eyespots that can help deter predators.

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Credit: Natalie Grace Schulz

Octopuses, squid and cuttlefish, collectively known as coleoid cephalopods, have evolved exceptionally large and elaborately structured nervous systems capable of complex behaviours such as problem-solving and rapid camouflage. A new study by scientists at The University of Vienna suggests that the origins of this complexity may lie not just in the genes themselves, but in how the genome is organised in 3D. The researchers found that ancient, extensive reorganisation of the genome altered how DNA is arranged inside the cell. These shifts brought previously distant regions of DNA into contact, changing the way genes are regulated. Understanding this process could change how we think about how new traits emerge during evolution. The findings are currently published in the renowned journal Nature Communications. 

The team studied the 3D structure of the genome across octopus, squid and cuttlefish, combining data on DNA structure with gene activity. "The genome isn't just a sequence of genes. It's folded into a complex three-dimensional structure," said lead author Dr Thea Rogers. "Understanding how that structure evolves is becoming increasingly important for understanding how new forms of biological complexity arise."

"Regulatory entanglement" as a consequence of genome reorganisation

In cephalopods, a large-scale burst of genome reorganisation, which occurred hundreds of millions of years ago, dramatically reshuffled the genome and brought previously distant regions of chromosomes into close proximity.

The researchers found that when regions of DNA are brought into contact, they can begin to interact and influence each other's activity. Over time, these interactions can become embedded, forming increasingly interconnected regulatory networks. 

"Regulatory entanglement" balances innovation and stability in genome evolution 

This process, described by the researchers as "regulatory entanglement", may allow genomes to generate new patterns of gene expression while maintaining essential functions. 

Not all aspects of genome structure appear to respond to genome reorganisation in the same way. The researchers found that large structural units of the genome, known as chromatin domains, remained largely stable over evolutionary time.

In contrast, finer-scale connections known as chromatin loops were far more dynamic. These loops bring distant regions of DNA into contact. They varied widely across species, tissues and developmental stages, and were often found near genes involved in key cephalopod traits, including those linked to the nervous system. This suggests that these more flexible regions may be particularly affected by large-scale changes in DNA organisation.

3D structure of DNA shapes evolutionary processes actively 

Together, these findings challenge the idea that genome architecture is a passive consequence of evolution. Instead, they suggest that the 3D organisation of DNA actively shapes how evolution unfolds. In cephalopods, this may have played a key role in the emergence of their unusually complex nervous systems.

Summary

• Scientists at the University of Vienna reconstructed the 3D organisation of the genome in octopus, squid and cuttlefish to investigate how genome architecture evolved following an ancient burst of genome reorganisation.
• The study found that this large-scale reorganisation brought previously distant regions of DNA into contact, creating new networks of regulatory interactions that became embedded over evolutionary time.
• The researchers describe this process as "regulatory entanglement", whereby new DNA interactions become increasingly interconnected, allowing genomes to generate novel patterns of gene regulation while maintaining essential biological functions.
• The researchers found that not all aspects of the 3D genome respond to genome reorganisation in the same way. Large chromatin domains remained remarkably stable, whereas finer-scale chromatin loops were far more dynamic.
• The findings challenge the view of genome architecture as a passive consequence of evolution and instead suggest that the 3D organisation of DNA can actively influence evolutionary change.

About the University of Vienna: 

For over 650 years the University of Vienna has stood for education, research and innovation. Today, it is ranked among the top 100 and thus the top four per cent of all universities worldwide and is globally connected. With degree programmes covering 188 disciplines, and approximately 11,000 employees, we are one of the largest academic institutions in Europe. Here, people from a broad spectrum of disciplines come together to carry out research at the highest level and develop solutions for current and future challenges. Its students and graduates develop reflected and sustainable solutions to complex challenges using innovative spirit and curiosity.

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Journal

Nature Communications

DOI

10.1038/s41467-026-77625-7

Article Title

Genome reorganisation and expansion shape 3D genome architecture and define a distinct regulatory landscape in coleoid cephalopods

Article Publication Date

9-Oct-2026

 

When AI chatbots give bad advice, no one can see the damage

New paper explores how chatbot health guidance leaves no trace for clinicians or regulators, and calls for transparency safeguards

Binghamton University

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As more and more people turn to AI chatbots for quick, 24/7 medical advice, a new perspective paper co-authored by faculty at Binghamton University, State University of New York explores the risks this practice carries that are largely invisible to users – and healthcare systems.

The paper, written by researchers at Binghamton University, Stanford University, Texas A&M University, and Indiana University, and published in Nature Health, examines what happens when a chatbot gives someone bad health advice. The authors argue that the harm is hard to catch because the conversation stays on the AI company's platform, the person has no place to report the problem, and outside researchers cannot measure the damage.

“We’re getting medical advice from these chatbots, but nobody—literally no one—is looking at this. If there’s an error or an issue, there’s just no way for people to know,” said Kaicheng Yang, an assistant professor in the School of Computing at Binghamton University’s Thomas J. Watson College of Engineering and Applied Science and one of the paper’s authors.

The researchers gave the example of a 60-year-old man who asked ChatGPT how to cut chloride from his diet and swapped table salt with sodium bromide. The man ended up being hospitalized with bromide toxicity after experiencing hallucinations and paranoia. The issue this paper highlights is that because the man received this advice from a chatbot and was unable to retrieve the conversation, his doctors had no way of knowing exactly what the man was told, making it nearly impossible to piece together exactly what happened.

Because there is no system of transparency in place for AI companies as it relates to the visibility of health advice it generates for patients, this paper asserts that this built-in, systemic lack of visibility is a key aspect of AI-generated health information because it actively prevents oversight. “Harms are not only possible, but structurally hidden from the clinicians, researchers, and regulators who could otherwise detect and correct them,” the authors note.

This paper also emphasizes a key facet of chatbots generating answers for people with health questions – they can be wrong. Chatbots can generate erroneous answers confidently, oversimplify information, or draw from outdated information/false claims. However, the authors also note that those risks can trickle down to those who are not actively seeking answers. With the prevalence of AI summaries in search engines and the integration of AI in social media platforms like X and Meta, you do not have to be actively searching for an answer to be given an incorrect bit of information.

“Sometimes I’m not even looking for health information, but just by browsing my social media feeds, it’s there. It just shows up, and we believe that could have undesirable outcomes, especially if there’s medical misinformation or state actors trying to manipulate the online discussion,” Yang said.

Regardless of whether a person is actively looking for answers or comes across them incidentally, the authors of this paper argue that the harm rarely leaves traces that clinicians, regulators, or researchers can verify.

To combat this, the authors propose several methods to increase transparency and responsibility for AI companies. They note that AI companies should give users access to their own health conversations to provide them the opportunity to share this information with clinicians so they can better investigate the pathway that led to a harmful event. They also recommend that those companies develop a disclosure system to allow health guidance to be flagged, reported, and investigated.

They further recommend that social media companies take more responsibility by enhancing clear labeling of AI-generated health content, withholding that content until it is vetted by medical governing bodies, and similarly, that search engines should only utilize vetted information in summaries. Policymakers, the authors suggest, should also extend physician malpractice liability to AI chatbot companies.

“We do not think this is something we should rely on the companies to do, because their incentive is always to make more money,” Yang said. “Building such a system goes against that incentive. So we have to have some kind of third-party monitoring system, an independent evaluation.”

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Journal

Nature Health

DOI

10.1038/s44360-026-00206-x

Method of Research

Commentary/editorial

Subject of Research

Not applicable

Article Title

The Invisible Risks of AI-Generated Health Information

Article Publication Date

9-Oct-2026

Introducing AlphaProof Nexus: An AI tool for formal mathematical proof discovery

Summary author: Walter Beckwith

American Association for the Advancement of Science (AAAS)

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A new large language model (LLM)-based artificial intelligence framework called AlphaProof Nexus can autonomously tackle select math problems, seeking proofs and using verification to ensure the resulting solutions are logically sound, researchers report. The system solved dozens of previously open problems across several mathematical fields, suggesting that artificial intelligence (AI) could become a useful tool for automated mathematical discovery and research. “[The authors report] that even unsuccessful proof attempts by AI could help them understand the problems better and make progress on solving them,” write Jeremy Avigad and Matthew Ballard in a related Perspective. “This underscores that an essential goal of developing AI for mathematics is to support mathematicians in the search for knowledge and understanding that lead to further advances.” Large language models (LLMs) have demonstrated growing ability to solve difficult mathematical problems, but their tendency to produce subtle logical errors or “hallucinations” makes them unreliable for research without extensive human expert review. One promising way to mitigate these issues is to have AI agents generate mathematical proofs in formal programming languages such as Lean, which automatically verifies each logical step and prevents errors from going unnoticed.  While this approach has been successfully applied to competition mathematics and in the human-aided formalization of natural language arguments, its potential in solving open research-level mathematical problems remains unknown.

 

To address this gap, George Tsoukalas and colleagues developed AlphaProof Nexus, a framework that uses multiple AI agents to search for mathematical proofs with feedback from the Lean compiler. Tsoukalas et al. also developed a more advanced, full-featured agent that coordinated subagents through an evolutionary algorithm to use AlphaProof as a specialized proof tool. In tests, the system was able to solve nine of the 353 attempted Erdős problems, including two that had remained unsolved for more than 50 years. It was also able to solve 44 of 492 open On-Line Encyclopedia of Integer Sequences (OEIS) conjectures as well as several other research-level problems in fields such as algebraic geometry, optimization, quantum optics, and graph theory.

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Journal

Science

DOI

10.1126/science.aej2213

Article Title

Advancing mathematics research with AI-driven formal proof search

Article Publication Date

8-Oct-2026

 

Study links pharmaceutical industry payments to changes in physicians’ prescribing practices

International researchers, including U of T Associate Professor Quinn Grundy find payments and gift relationships often lead physicians to more expensive, less appropriate drugs

University of Toronto

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A new Cochrane review led by a team of international researchers including from U of T, has found that marketing strategies used by pharmaceutical companies such as payments for consulting and advisory board membership and free meals offered to physicians, can negatively influence prescribing habits.

The review compiled data from over 93 studies and included observed practices of millions of prescribers who had received either advertising and education, such as sales rep visits, gifts and payments, or free samples from pharmaceutical companies. The researchers found that these gift relationships and marketing tactics led physicians to more often prescribe the drugs a company was promoting. The data also showed that these marketing practices were strongly linked to inappropriate prescribing, meaning physicians were likely prescribing treatments that patients do not necessarily need, or that may cause harm.

Quinn Grundy is an associate professor at the Lawrence Bloomberg Faculty of Nursing and is one of the two Canadian authors involved in the review.  She points out that these marketing tactics employed by pharmaceutical companies are a common practice among physicians globally, with the same multi-national companies marketing their drugs worldwide.

“In the U.S., where companies are required to report payments made to physicians in a public database, just over half of all licensed physicians have accepted a payment, including free meals from a pharmaceutical company,” says Grundy, who is also the Director of the WHO Collaborating Centre for Governance, Accountability, and Transparency in the Pharmaceutical Sector located at the University of Toronto.  “This is important because it shows that companies are focusing their marketing resources on physicians who will deliver the highest return on investment, and prescribe more of their promoted drug, but it also shows that there are a large number of physicians who are choosing not to interact with pharmaceutical companies and remain independent of these influences.”

There were no Canadian studies included in the review, in part because Canada does not have a mechanism in place to track how much or why pharmaceutical companies are paying physicians or nurse practitioners. However, Grundy notes that according to surveys and qualitative research not included in this review, free meals and payments are likely common among Canadian prescribers.

“When physicians accept payments or free meals from the pharmaceutical industry we can see evidence in the data that physicians prescribe more of the promoted drug. This practice can increase the overall costs to our health system, and to patients through higher co-pays and out-of-pocket costs, when they are prescribed a brand name drug even though cost-effective alternatives exist,” says Grundy.

Grundy believes it is imperative that healthcare organizations, professional societies, and health professional schools be more aware of the influence of pharmaceutical industry promotion and address these through policy changes.

“Prescribers need independent, evidence-based sources of information to ensure their own independence in practice and to be trustworthy and accountable to the people they serve,” says Grundy.

Studies included in the review also examined the impact of conflict-of-interest policies or limitations on physician interactions with industry in the practice setting such as within medical schools and teaching hospitals. The review showed that in these instances, conflict-of-interest policies had a mitigating effect where physicians tended to prescribe less overall or prescribed more appropriate treatments. The review authors suggest that more robust conflict-of-interest policies would be an important way forward to reduce the influence of pharma on prescribers.

“These studies show that we can create practice environments that promote and preserve independence and that this is best achieved collectively, within health systems and institutions, rather than leaving it up to individual clinicians,” says Grundy.

While the available research focused on physicians in many health systems, including Canada, physicians are no longer the only prescribers. Other descriptive studies using the Open Payments data in the U.S., and which were not included in this review, found that advanced practice nurses, including nurse practitioners and clinical nurse specialists, are also targets of industry promotion.

“This is not just a problem for medicine, it affects the entire healthcare team,” says Grundy. “We need to create healthcare environments that safeguard the independence and integrity of care.”

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Journal

Cochrane Database of Systematic Reviews

DOI

10.1002/14651858.CD013423.pub3

Article Title

Pharmaceutical industry information and promotional strategies aimed at prescribers

Article Publication Date

9-Oct-2026

Pharmaceutical company marketing negatively influences prescribing

Doctors’ prescribing habits are heavily influenced by payments, gifts, and free meals from pharmaceutical companies, leading to more expensive, less appropriate and more drugs being prescribed, a new Cochrane review finds

Cochrane

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This infographic details the number of meals received in 2014 versus opioid prescribing in 2015, based on Hadland et al. (2018). It visualises the meals received by physicians and the subsequent prescribing rates.

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Credit: Peter Homer, Creative Content Producer, Cochrane

Doctors’ prescribing habits are heavily influenced by payments, gifts, and free meals from pharmaceutical companies, leading to more expensive, less appropriate and more drugs being prescribed, a new Cochrane review finds. This can seriously harm both individual patients and health systems.

Pharmaceutical companies use a variety of strategies to market and promote their drugs. This can include one-on-one visits by sales reps to doctors' offices and hospitals, gifts and payments including for example paid meals, travel costs to conferences, entertainment, consulting fees, honoraria for participation in advisory boards, and advertising.

For all new medicines, pharmaceutical companies target prescribers with offers of free meals and other gifts and payments. These payments and gifts lead to prescribing of the company's promoted drug, which may not always be needed or be the most appropriate or affordable medicine for each patient.

Less appropriate prescribing and higher medicine costs

The review included 93 studies involving a number of different study types. Almost all of these studies observed real-world prescribing patterns rather than running controlled experiments. The majority of the studies (88%) came from the United States, in part because the Sunshine Act (2010) requires pharmaceutical companies to publicly report details of all payments to doctors, which are compiled in a publicly searchable and analyzable database.

Analyzing millions of prescribers, the authors grouped industry interactions into three distinct categories to examine how each one affects a doctor's prescribing habits. These were advertising and education, gifts and payments, and free samples. The authors also looked at conflict-of-interest policies as a mitigation strategy.

Advertising and education, such as sales rep visits, seemed linked to prescribing that was less clinically suitable and pricier, with fairly strong evidence that it also drove up prescription volume.

The largest and most consistent body of evidence covered gifts and payments. Gifts and payments were also linked to less appropriate prescribing, more prescriptions, and probably increased costs.

The evidence was too sparse or weak to draw clear conclusions on free drug samples and whether promotion affects hospitals’ approved formularies, although what little exists suggests it might.

“Overall, when doctors have more contact with drug company promotion, prescribing tends to become less appropriate, more frequent, and more expensive”, says study author Dr Lisa Bero from the University of Colorado Anschutz, USA. “This is problematic for a number of reasons and it matters because it directly affects patient care. These less appropriate, more expensive drugs can have fewer benefits or more side-effects than alternatives, or simply be unnecessary in the clinical context.”

The overprescription of opioids is the most infamous example of pharmaceutical companies’ promotion exaggerating benefits and minimizing harms. This review found that even inexpensive meals increased opioid prescribing and that the more payments a doctor received from opioid manufacturers, the more likely they were to prescribe dangerously high opioid doses. The widespread inappropriate overprescribing of opioids has led to an epidemic of addiction and deaths from overdoses.

“Patients should be offered the most appropriate treatment for their condition, based on clinical evidence not industry marketing,” adds Dr Bero. “The opioid crisis in North America was perhaps the most egregious example of inappropriate over-prescribing, but this was not an isolated incident. It was high-profile due to the significant harms involved, but the systems that enabled it are unfortunately considered business-as-usual within the industry. Interactions between pharmaceutical companies and prescribing physicians are widespread, and the harms they cause are rarely so visible.”

More meals paid for, more drugs prescribed

Notably, the research shows a clear dose-response relationship between paid-for meals and inappropriate prescriptions. The more meals a doctor received from a company, the more of the company's drug they prescribed. This was true for a range of different types of drugs, from drugs for high blood pressure and cholesterol to antidepressants and opioid painkillers.

The authors also point out that this practice is seen as normal and unproblematic in the medical field.  

“It's very common for doctors to receive free meals from companies,” says lead author, Dr Barbara Mintzes from the University of Sydney, Australia. “Doctors often think that this is trivial and doesn’t influence them, that they ‘can’t be bought for the price of a sandwich’, but the data shows this is an effective marketing strategy. The more free meals a doctor receives, the more likely they are to prescribe less appropriate or more expensive drugs.”

Restricting industry interactions may improve prescribing

Some hospitals and medical centres have rules or institutional restrictions in place, also known as conflict-of-interest policies, to limit how much contact industry reps can have with doctors or what gifts or samples they are allowed to provide. The review found that these can mitigate the negative impact of pharma strategies on doctors’ prescribing habits.

“It’s encouraging to see that robust conflict-of-interest policies in place tended to be effective,” Dr Mintzes says. “The data shows that they probably improve prescribing appropriateness and possibly reduce the number of prescriptions.”

While this review found that drug promotion negatively influences prescribing within a broad range of drugs and clinical settings, the authors wish to emphasize that  this is not about a few "bad apples”, but about improving the system and a key positive finding is that strict conflict-of-interest policies are a way forward.

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Journal

Cochrane Database of Systematic Reviews

DOI

10.1002/14651858.CD013423.pub3

Method of Research

Systematic review

Subject of Research

People

Article Title

Pharmaceutical industry information and promotional strategies aimed at prescribers

Article Publication Date

8-Oct-2026

COI Statement

Barbara Mintzes (BM): BM is a member of Health Action International (HAI-Europe Association) and the Therapeutics Initiative. She is an Associate Editor with UK Drug & Therapeutics Bulletin, and serves as General Secretary for the International Society of Drug Bulletins (ISDB) from 2023 to 2028. These organisations produce independent information on medicines and do not receive any funding from the pharmaceutical industry. She hasalso acted as an expert witness for Health Canada and for Australia's Therapeutic Goods Administration. Alice Fabbri (AF): AF is currently working as a public health physician at the Hygiene and Public Health Unit in Ravenna, Department of Public Health, Azienda Sanitaria Locale (AUSL) Romagna, Italy. Quinn Grundy (QG): QG served as consultant to the Government of Canada Competition Bureau in 2025. Geoffrey Spurling (GS): none known Joel Lexchin (JL): Between 2023-2026, Joel Lexchin received payments for writing a brief for a legal fi rm on the role of promotion in generating prescriptions for opioids and for co-writing an article for a peer-reviewed medical journal on semaglutide. He is a member of the Board of the Canadian Health Coalition. He receives royalties from University of Toronto Press and James Lorimer & Co. Ltd. for books he has written. He has received funding from the Canadian Institutes of Health Research in the past. Riaz Qureshi (RQ): RQ is faculty with Cochrane Eyes and Vision, which has no relation to this review topic. RQ was not funded for the work on this article. Lisa Bero (LB): LB is Research Integrity Editor, Cochrane, for which she receives payment. She was not involved in the editorial process for this article. LB, BM, QG, AF, and JS were authors of studies screened for eligibility for inclusion. They were not involved in screening studies which they authored. None of the included studies were authored by any of the review authors.