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“Dr. Google” had its issues. Can ChatGPT Health do better?

For the past two decades, there’s been a clear first step for anyone who starts experiencing new medical symptoms: Look them up online. The practice was so common that it gained the pejorative moniker “Dr. Google.” But times are changing, and many medical-information seekers are now using LLMs. According to OpenAI, 230 million people ask ChatGPT health-related queries each week. 

That’s the context around the launch of OpenAI’s new ChatGPT Health product, which debuted earlier this month. It landed at an inauspicious time: Two days earlier, the news website SFGate had broken the story of Sam Nelson, a teenager who died of an overdose last year after extensive conversations with ChatGPT about how best to combine various drugs. In the wake of both pieces of news, multiple journalists questioned the wisdom of relying for medical advice on a tool that could cause such extreme harm.

Though ChatGPT Health lives in a separate sidebar tab from the rest of ChatGPT, it isn’t a new model. It’s more like a wrapper that provides one of OpenAI’s preexisting models with guidance and tools it can use to provide health advice—including some that allow it to access a user’s electronic medical records and fitness app data, if granted permission. There’s no doubt that ChatGPT and other large language models can make medical mistakes, and OpenAI emphasizes that ChatGPT Health is intended as an additional support, rather than a replacement for one’s doctor. But when doctors are unavailable or unable to help, people will turn to alternatives. 

Some doctors see LLMs as a boon for medical literacy. The average patient might struggle to navigate the vast landscape of online medical information—and, in particular, to distinguish high-quality sources from polished but factually dubious websites—but LLMs can do that job for them, at least in theory. Treating patients who had searched for their symptoms on Google required “a lot of attacking patient anxiety [and] reducing misinformation,” says Marc Succi, an associate professor at Harvard Medical School and a practicing radiologist. But now, he says, “you see patients with a college education, a high school education, asking questions at the level of something an early med student might ask.”

The release of ChatGPT Health, and Anthropic’s subsequent announcement of new health integrations for Claude, indicate that the AI giants are increasingly willing to acknowledge and encourage health-related uses of their models. Such uses certainly come with risks, given LLMs’ well-documented tendencies to agree with users and make up information rather than admit ignorance. 

But those risks also have to be weighed against potential benefits. There’s an analogy here to autonomous vehicles: When policymakers consider whether to allow Waymo in their city, the key metric is not whether its cars are ever involved in accidents but whether they cause less harm than the status quo of relying on human drivers. If Dr. ChatGPT is an improvement over Dr. Google—and early evidence suggests it may be—it could potentially lessen the enormous burden of medical misinformation and unnecessary health anxiety that the internet has created.

Pinning down the effectiveness of a chatbot such as ChatGPT or Claude for consumer health, however, is tricky. “It’s exceedingly difficult to evaluate an open-ended chatbot,” says Danielle Bitterman, the clinical lead for data science and AI at the Mass General Brigham health-care system. Large language models score well on medical licensing examinations, but those exams use multiple-choice questions that don’t reflect how people use chatbots to look up medical information.

Sirisha Rambhatla, an assistant professor of management science and engineering at the University of Waterloo, attempted to close that gap by evaluating how GPT-4 responded to licensing exam questions when it did not have access to a list of possible answers. Medical experts who evaluated the responses scored only about half of them as entirely correct. But multiple-choice exam questions are designed to be tricky enough that the answer options don’t give them entirely away, and they’re still a pretty distant approximation for the sort of thing that a user would type into ChatGPT.

A different study, which tested GPT-4o on more realistic prompts submitted by human volunteers, found that it answered medical questions correctly about 85% of the time. When I spoke with Amulya Yadav, an associate professor at Pennsylvania State University who runs the Responsible AI for Social Emancipation Lab and led the study, he made it clear that he wasn’t personally a fan of patient-facing medical LLMs. But he freely admits that, technically speaking, they seem up to the task—after all, he says, human doctors misdiagnose patients 10% to 15% of the time. “If I look at it dispassionately, it seems that the world is gonna change, whether I like it or not,” he says.

For people seeking medical information online, Yadav says, LLMs do seem to be a better choice than Google. Succi, the radiologist, also concluded that LLMs can be a better alternative to web search when he compared GPT-4’s responses to questions about common chronic medical conditions with the information presented in Google’s knowledge panel, the information box that sometimes appears on the right side of the search results.

Since Yadav’s and Succi’s studies appeared online, in the first half of 2025, OpenAI has released multiple new versions of GPT, and it’s reasonable to expect that GPT-5.2 would perform even better than its predecessors. But the studies do have important limitations: They focus on straightforward, factual questions, and they examine only brief interactions between users and chatbots or web search tools. Some of the weaknesses of LLMs—most notably their sycophancy and tendency to hallucinate—might be more likely to rear their heads in more extensive conversations and with people who are dealing with more complex problems. Reeva Lederman, a professor at the University of Melbourne who studies technology and health, notes that patients who don’t like the diagnosis or treatment recommendations that they receive from a doctor might seek out another opinion from an LLM—and the LLM, if it’s sycophantic, might encourage them to reject their doctor’s advice.

Some studies have found that LLMs will hallucinate and exhibit sycophancy in response to health-related prompts. For example, one study showed that GPT-4 and GPT-4o will happily accept and run with incorrect drug information included in a user’s question. In another, GPT-4o frequently concocted definitions for fake syndromes and lab tests mentioned in the user’s prompt. Given the abundance of medically dubious diagnoses and treatments floating around the internet, these patterns of LLM behavior could contribute to the spread of medical misinformation, particularly if people see LLMs as trustworthy.

OpenAI has reported that the GPT-5 series of models is markedly less sycophantic and prone to hallucination than their predecessors, so the results of these studies might not apply to ChatGPT Health. The company also evaluated the model that powers ChatGPT Health on its responses to health-specific questions, using their publicly available HeathBench benchmark. HealthBench rewards models that express uncertainty when appropriate, recommend that users seek medical attention when necessary, and refrain from causing users unnecessary stress by telling them their condition is more serious that it truly is. It’s reasonable to assume that the model underlying ChatGPT Health exhibited those behaviors in testing, though Bitterman notes that some of the prompts in HealthBench were generated by LLMs, not users, which could limit how well the benchmark translates into the real world.

An LLM that avoids alarmism seems like a clear improvement over systems that have people convincing themselves they have cancer after a few minutes of browsing. And as large language models, and the products built around them, continue to develop, whatever advantage Dr. ChatGPT has over Dr. Google will likely grow. The introduction of ChatGPT Health is certainly a move in that direction: By looking through your medical records, ChatGPT can potentially gain far more context about your specific health situation than could be included in any Google search, although numerous experts have cautioned against giving ChatGPT that access for privacy reasons.

Even if ChatGPT Health and other new tools do represent a meaningful improvement over Google searches, they could still conceivably have a negative effect on health overall. Much as automated vehicles, even if they are safer than human-driven cars, might still prove a net negative if they encourage people to use public transit less, LLMs could undermine users’ health if they induce people to rely on the internet instead of human doctors, even if they do increase the quality of health information available online.

Lederman says that this outcome is plausible. In her research, she has found that members of online communities centered on health tend to put their trust in users who express themselves well, regardless of the validity of the information they are sharing. Because ChatGPT communicates like an articulate person, some people might trust it too much, potentially to the exclusion of their doctor. But LLMs are certainly no replacement for a human doctor—at least not yet.

Correction 1/26: A previous version of this story incorrectly referred to the version of ChatGPT that Rambhatla evaluated. It was GPT-4, not GPT-4o.

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The Responsibility Vacuum: Organizational Failure in Scaled Agent Systems

arXiv:2601.15059v1 Announce Type: new Abstract: Modern CI/CD pipelines integrating agent-generated code exhibit a structural failure in responsibility attribution. Decisions are executed through formally correct approval processes, yet no entity possesses both the authority to approve those decisions and the epistemic capacity to meaningfully understand their basis. We define this condition as responsibility vacuum: a state in which decisions occur, but responsibility cannot be attributed because authority and verification capacity do not coincide. We show that this is not a process deviation or technical defect, but a structural property of deployments where decision generation throughput exceeds bounded human verification capacity. We identify a scaling limit under standard deployment assumptions, including parallel agent generation, CI-based validation, and individualized human approval gates. Beyond a throughput threshold, verification ceases to function as a decision criterion and is replaced by ritualized approval based on proxy signals. Personalized responsibility becomes structurally unattainable in this regime. We further characterize a CI amplification dynamic, whereby increasing automated validation coverage raises proxy signal density without restoring human capacity. Under fixed time and attention constraints, this accelerates cognitive offloading in the broad sense and widens the gap between formal approval and epistemic understanding. Additional automation therefore amplifies, rather than mitigates, the responsibility vacuum. We conclude that unless organizations explicitly redesign decision boundaries or reassign responsibility away from individual decisions toward batch- or system-level ownership, responsibility vacuum remains an invisible but persistent failure mode in scaled agent deployments.
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Guardrails for trust, safety, and ethical development and deployment of Large Language Models (LLM)

arXiv:2601.14298v1 Announce Type: cross Abstract: The AI era has ushered in Large Language Models (LLM) to the technological forefront, which has been much of the talk in 2023, and is likely to remain as such for many years to come. LLMs are the AI models that are the power house behind generative AI applications such as ChatGPT. These AI models, fueled by vast amounts of data and computational prowess, have unlocked remarkable capabilities, from human-like text generation to assisting with natural language understanding (NLU) tasks. They have quickly become the foundation upon which countless applications and software services are being built, or at least being augmented with. However, as with any groundbreaking innovations, the rise of LLMs brings forth critical safety, privacy, and ethical concerns. These models are found to have a propensity to leak private information, produce false information, and can be coerced into generating content that can be used for nefarious purposes by bad actors, or even by regular users unknowingly. Implementing safeguards and guardrailing techniques is imperative for applications to ensure that the content generated by LLMs are safe, secure, and ethical. Thus, frameworks to deploy mechanisms that prevent misuse of these models via application implementations is imperative. In this study, wepropose a Flexible Adaptive Sequencing mechanism with trust and safety modules, that can be used to implement safety guardrails for the development and deployment of LLMs.
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Towards Execution-Grounded Automated AI Research

arXiv:2601.14525v1 Announce Type: cross Abstract: Automated AI research holds great potential to accelerate scientific discovery. However, current LLMs often generate plausible-looking but ineffective ideas. Execution grounding may help, but it is unclear whether automated execution is feasible and whether LLMs can learn from the execution feedback. To investigate these, we first build an automated executor to implement ideas and launch large-scale parallel GPU experiments to verify their effectiveness. We then convert two realistic research problems - LLM pre-training and post-training - into execution environments and demonstrate that our automated executor can implement a large fraction of the ideas sampled from frontier LLMs. We analyze two methods to learn from the execution feedback: evolutionary search and reinforcement learning. Execution-guided evolutionary search is sample-efficient: it finds a method that significantly outperforms the GRPO baseline (69.4% vs 48.0%) on post-training, and finds a pre-training recipe that outperforms the nanoGPT baseline (19.7 minutes vs 35.9 minutes) on pre-training, all within just ten search epochs. Frontier LLMs often generate meaningful algorithmic ideas during search, but they tend to saturate early and only occasionally exhibit scaling trends. Reinforcement learning from execution reward, on the other hand, suffers from mode collapse. It successfully improves the average reward of the ideator model but not the upper-bound, due to models converging on simple ideas. We thoroughly analyze the executed ideas and training dynamics to facilitate future efforts towards execution-grounded automated AI research.
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Automated Rubrics for Reliable Evaluation of Medical Dialogue Systems

arXiv:2601.15161v1 Announce Type: cross Abstract: Large Language Models (LLMs) are increasingly used for clinical decision support, where hallucinations and unsafe suggestions may pose direct risks to patient safety. These risks are particularly challenging as they often manifest as subtle clinical errors that evade detection by generic metrics, while expert-authored fine-grained rubrics remain costly to construct and difficult to scale. In this paper, we propose a retrieval-augmented multi-agent framework designed to automate the generation of instance-specific evaluation rubrics. Our approach grounds evaluation in authoritative medical evidence by decomposing retrieved content into atomic facts and synthesizing them with user interaction constraints to form verifiable, fine-grained evaluation criteria. Evaluated on HealthBench, our framework achieves a Clinical Intent Alignment (CIA) score of 60.12%, a statistically significant improvement over the GPT-4o baseline (55.16%). In discriminative tests, our rubrics yield a mean score delta ($\mu_{\Delta} = 8.658$) and an AUROC of 0.977, nearly doubling the quality separation achieved by GPT-4o baseline (4.972). Beyond evaluation, our rubrics effectively guide response refinement, improving quality by 9.2% (from 59.0% to 68.2%). This provides a scalable and transparent foundation for both evaluating and improving medical LLMs. The code is available at https://anonymous.4open.science/r/Automated-Rubric-Generation-AF3C/.
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Towards AI Transparency and Accountability: A Global Framework for Exchanging Information on AI Systems

arXiv:2307.13658v3 Announce Type: replace-cross Abstract: We propose that future AI transparency and accountability regulations are based on an open global standard for exchanging information about AI systems, which allows co-existence of potentially conflicting local regulations. Then, we discuss key components of a lightweight and effective AI transparency and/or accountability regulation. To prevent overregulation, the proposed approach encourages collaboration between regulators and industry to create a scalable and cost-efficient mutually beneficial solution. This includes using automated assessments and benchmarks with results transparently communicated through AI cards in an open AI register to facilitate meaningful public comparisons of competing AI systems. Such AI cards should report standardized measures tailored to the specific high-risk applications of AI systems and could be used for conformity assessments under AI transparency and accountability policies such as the European Union's AI Act.
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PPGFlowECG: Latent Rectified Flow with Cross-Modal Encoding for PPG-Guided ECG Generation and Cardiovascular Disease Detection

arXiv:2509.19774v2 Announce Type: replace-cross Abstract: Electrocardiography (ECG) is the clinical gold standard for cardiovascular disease (CVD) assessment, yet continuous monitoring is constrained by the need for dedicated hardware and trained personnel. Photoplethysmography (PPG) is ubiquitous in wearable devices and readily scalable, but it lacks electrophysiological specificity, limiting diagnostic reliability. While generative methods aim to translate PPG into clinically useful ECG signals, existing approaches are limited by the misalignment of physiological semantics in generative models and the complexity of modeling in high-dimensional signals. To address these limitations, we propose PPGFlowECG, a two-stage framework that aligns PPG and ECG in a shared latent space using the CardioAlign Encoder and then synthesizes ECGs with latent rectified flow. We further provide a formal analysis of this coupling, showing that the CardioAlign Encoder is necessary to guarantee stable and semantically consistent ECG synthesis under our formulation. Extensive experiments on four datasets demonstrate improved synthesis fidelity and downstream diagnostic utility. These results indicate that PPGFlowECG supports scalable, wearable-first CVD screening when standard ECG acquisition is unavailable.
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Large language models improve transferability of electronic health record-based predictions across countries and coding systems

npj Digital Medicine, Published online: 22 January 2026; doi:10.1038/s41746-026-02363-5

Large language models improve transferability of electronic health record-based predictions across countries and coding systems
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Multimodal AI generates virtual population for tumor microenvironment modeling

GigaTIME leverages multimodal AI to generate virtual multiplex immunofluorescence (mIF) profiles from standard H&E slides, enabling comprehensive tumor immune microenvironment modeling across a large (>14,000) and diverse patient population. This virtual approach unlocks new opportunities for large-scale clinical discoveries that were previously hindered by the scarcity of mIF data.
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Research progress in diagnosis and treatment of pancreatic cancer with mismatch repair and microsatellite instability

Clin Transl Oncol. 2026 Jan 21. doi: 10.1007/s12094-025-04214-3. Online ahead of print.

ABSTRACT

Pancreatic cancer (PC), predominantly pancreatic ductal adenocarcinoma, remains one of the most lethal malignancies, largely due to late diagnosis and intrinsic resistance to conventional therapies. In recent years, mismatch repair deficiency (dMMR) and microsatellite instability-high (MSI-H) have emerged as clinically actionable biomarkers in a small but distinct subset of PC, accounting for approximately 1-2% of cases. These tumors display unique molecular characteristics, including a high prevalence of wild-type KRAS and TP53, elevated tumor mutational burden, and recurrent kinase fusions, which together confer enhanced immunogenicity and increased sensitivity to immune checkpoint inhibitors (ICIs). In addition to their therapeutic relevance, dMMR/MSI-H status has important diagnostic implications for the identification of Lynch syndrome-associated pancreatic cancers, informing genetic counseling and familial risk assessment. This review summarizes current understanding of the molecular basis of mismatch repair deficiency and microsatellite instability in PC, evaluates available diagnostic approaches such as immunohistochemistry, polymerase chain reaction, and next-generation sequencing, and discusses the prognostic and predictive significance of dMMR/MSI-H status. Emerging clinical evidence supporting the use of ICIs in selected patients across neoadjuvant, adjuvant, and advanced disease settings is also reviewed, along with challenges related to assay discordance, tumor heterogeneity, and immunotherapy resistance. Finally, future directions are highlighted, emphasizing the need for standardized testing algorithms, integration of multi-omics and spatial profiling technologies, and prospective clinical studies to optimize precision treatment strategies for this rare but clinically meaningful subtype of pancreatic cancer.

PMID:41563663 | DOI:10.1007/s12094-025-04214-3

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Everyone wants AI sovereignty. No one can truly have it.

Governments plan to pour $1.3 trillion into AI infrastructure by 2030 to invest in “sovereign AI,” with the premise being that countries should be in control of their own AI capabilities. The funds include financing for domestic data centers, locally trained models, independent supply chains, and national talent pipelines. This is a response to real shocks: covid-era supply chain breakdowns, rising geopolitical tensions, and the war in Ukraine.  

But the pursuit of absolute autonomy is running into reality. AI supply chains are irreducibly global: Chips are designed in the US and manufactured in East Asia; models are trained on data sets drawn from multiple countries; applications are deployed across dozens of jurisdictions.  

If sovereignty is to remain meaningful, it must shift from a defensive model of self-reliance to a vision that emphasizes the concept of orchestration, balancing national autonomy with strategic partnership. 

Why infrastructure-first strategies hit walls 

A November survey by Accenture found that 62% of European organizations are now seeking sovereign AI solutions, driven primarily by geopolitical anxiety rather than technical necessity. That figure rises to 80% in Denmark and 72% in Germany. The European Union has appointed its first Commissioner for Tech Sovereignty. 

This year, $475 billion is flowing into AI data centers globally. In the United States, AI data centers accounted for roughly one-fifth of GDP growth in the second quarter of 2025. But the obstacle for other nations hoping to follow suit isn’t just money. It’s energy and physics. Global data center capacity is projected to hit 130 gigawatts by 2030, and for every $1 billion spent on these facilities, $125 million is needed for electricity networks. More than $750 billion in planned investment is already facing grid delays. 

And it’s also talent. Researchers and entrepreneurs are mobile, drawn to ecosystems with access to capital, competitive wages, and rapid innovation cycles. Infrastructure alone won’t attract or retain world-class talent.  

What works: An orchestrated sovereignty

What nations need isn’t sovereignty through isolation but through specialization and orchestration. This means choosing which capabilities you build, which you pursue through partnership, and where you can genuinely lead in shaping the global AI landscape. 

The most successful AI strategies don’t try to replicate Silicon Valley; they identify specific advantages and build partnerships around them. 

Singapore offers a model. Rather than seeking to duplicate massive infrastructure, it invested in governance frameworks, digital-identity platforms, and applications of AI in logistics and finance, areas where it can realistically compete. 

Israel shows a different path. Its strength lies in a dense network of startups and military-adjacent research institutions delivering outsize influence despite the country’s small size. 

South Korea is instructive too. While it has national champions like Samsung and Naver, these firms still partner with Microsoft and Nvidia on infrastructure. That’s deliberate collaboration reflecting strategic oversight, not dependence.  

Even China, despite its scale and ambition, cannot secure full-stack autonomy. Its reliance on global research networks and on foreign lithography equipment, such as extreme ultraviolet systems needed to manufacture advanced chips and GPU architectures, shows the limits of techno-nationalism. 

The pattern is clear: Nations that specialize and partner strategically can outperform those trying to do everything alone. 

Three ways to align ambition with reality 

1.  Measure added value, not inputs.  

Sovereignty isn’t how many petaflops you own. It’s how many lives you improve and how fast the economy grows. Real sovereignty is the ability to innovate in support of national priorities such as productivity, resilience, and sustainability while maintaining freedom to shape governance and standards.  

Nations should track the use of AI in health care and monitor how the technology’s adoption correlates with manufacturing productivity, patent citations, and international research collaborations. The goal is to ensure that AI ecosystems generate inclusive and lasting economic and social value.  

2. Cultivate a strong AI innovation ecosystem. 

Build infrastructure, but also build the ecosystem around it: research institutions, technical education, entrepreneurship support, and public-private talent development. Infrastructure without skilled talent and vibrant networks cannot deliver a lasting competitive advantage.   

3. Build global partnerships.  

Strategic partnerships enable nations to pool resources, lower infrastructure costs, and access complementary expertise. Singapore’s work with global cloud providers and the EU’s collaborative research programs show how nations advance capabilities faster through partnership than through isolation. Rather than competing to set dominant standards, nations should collaborate on interoperable frameworks for transparency, safety, and accountability.  

What’s at stake 

Overinvesting in independence fragments markets and slows cross-border innovation, which is the foundation of AI progress. When strategies focus too narrowly on control, they sacrifice the agility needed to compete. 

The cost of getting this wrong isn’t just wasted capital—it’s a decade of falling behind. Nations that double down on infrastructure-first strategies risk ending up with expensive data centers running yesterday’s models, while competitors that choose strategic partnerships iterate faster, attract better talent, and shape the standards that matter. 

The winners will be those who define sovereignty not as separation, but as participation plus leadership—choosing who they depend on, where they build, and which global rules they shape. Strategic interdependence may feel less satisfying than independence, but it’s real, it is achievable, and it will separate the leaders from the followers over the next decade. 

The age of intelligent systems demands intelligent strategies—ones that measure success not by infrastructure owned, but by problems solved. Nations that embrace this shift won’t just participate in the AI economy; they’ll shape it. That’s sovereignty worth pursuing. 

Cathy Li is head of the Centre for AI Excellence at the World Economic Forum.

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Communication Strategies to Promote Patient Engagement in Telemedicine: Systematic Review

Background: The rapid growth of telemedicine offers convenience, flexibility, and accessibility for patients to have health care services worldwide. To succeed in telemedicine, health care practitioners and telemedicine tools must engage patients through effective communication. However, a research gap exists in understanding the communication strategies used in telemedicine and how they effectively engage patients. Objective: This study aims to identify communication strategies influencing patient engagement in telemedicine with provider-patient interactions, as well as how included studies evaluate patient engagement through a systematic review. Methods: We searched the literature comprehensively using 6 databases, Web of Science, PubMed, Scopus, MEDLINE, CINAHL, and Embase, from inception to October 2025. We included empirical, English-language studies that examined communication strategies affecting patient engagement in telemedicine with provider-patient interactions. Studies lacking actual patients or provider-patient interactions in telemedicine were excluded. We used content analysis to identify texts that were related to Theme 1: the communication strategies affecting patient engagement, and Theme 2: evaluation of patient engagement. Coded texts were analyzed to develop subthemes and themes of identified communication strategies. Methods for evaluating patient engagement were summarized. A narrative synthesis was conducted because of heterogeneity across study design and outcomes. We used the Mixed Methods Appraisal Tool to assess the quality of research included in this study. Results: This study systematically reviewed 34 peer-reviewed articles, revealing 3 overarching themes of effective communication strategies that enhance patient engagement: interpersonal communication strategies, with 6 subthemes (building relationships, supportive attitude, interactive dialogic loop, nonverbal communication, professionalism and accuracy, and tailored communication); team-level communication strategies, with 3 subthemes (training and preparation, teamwork and care coordination, and cultural and linguistic sensitivity); and system-level communication strategies, with 3 subthemes (usefulness of information, ease of use, and data privacy and security). We also found that included studies predominantly used qualitative research methods, such as semistructured interviews and focus groups, to collect patient engagement data. Conclusions: This review provides an innovative synthesis of communication strategies that promote patient engagement in telemedicine by integrating interpersonal (micro), team (meso), and system-level (macro) perspectives. Unlike previous reviews that focused on single aspects or levels of communication, this study offers a holistic framework that advances theoretical understanding of how multilevel communication strategies collectively shape patient engagement. Practically, the findings offer actionable guidance for health care professionals, telemedicine developers, and policymakers seeking to enhance the quality and sustainability of telemedicine services. In real-world settings, the identified strategies can inform professional training, platform design, and policy development to support patient-centered digital care. This review is the first to systematically bring together communication strategies for patient engagement in telemedicine across all 3 levels. Future research should build on this framework by developing and validating quantitative measures of patient engagement and examining the relationships between communication strategies and telemedicine outcomes.
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United multi-omics and machine learning refine regulatory T cell-defined hepatocellular carcinoma subtypes

iScience. 2025 Dec 3;29(1):114328. doi: 10.1016/j.isci.2025.114328. eCollection 2026 Jan 16.

ABSTRACT

Hepatocellular carcinoma (HCC) is highly heterogeneous and aggressive, and the absence of precision individual treatment regimen enables repeated immune escape. Exploiting regulatory T cell (Treg) marker genes as key classifiers, we used 10 clustering algorithms to integrate the multi-omics HCC patient data and combined them with 10 machine learning (ML) algorithms to delineate molecular subtypes predictive of prognosis and immune response. We identified two cancer subtypes (CSs) that are associated with prognosis, with the second subtype (CS2) showing the most favorable prognostic outcomes. Subsequently, 9 key genes were screened for HCC model scoring, stratifying patients into low-risk (good prognosis, responsive to immunotherapy) and high-risk (poor outcome, not responsive to immunotherapy) groups. The high-risk group may be effective against the mTOR inhibitor AZD8055. Comprehensive multi-omics data and multiple ML algorithms offer key insights into HCC occurrence and evolution, with model scores guiding patient prognosis and treatment clinically.

PMID:41561382 | PMC:PMC12814435 | DOI:10.1016/j.isci.2025.114328

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Responsible AI for General-Purpose Systems: Overview, Challenges, and A Path Forward

arXiv:2601.13122v1 Announce Type: new Abstract: Modern general-purpose AI systems made using large language and vision models, are capable of performing a range of tasks like writing text articles, generating and debugging codes, querying databases, and translating from one language to another, which has made them quite popular across industries. However, there are risks like hallucinations, toxicity, and stereotypes in their output that make them untrustworthy. We review various risks and vulnerabilities of modern general-purpose AI along eight widely accepted responsible AI (RAI) principles (fairness, privacy, explainability, robustness, safety, truthfulness, governance, and sustainability) and compare how they are non-existent or less severe and easily mitigable in traditional task-specific counterparts. We argue that this is due to the non-deterministically high Degree of Freedom in output (DoFo) of general-purpose AI (unlike the deterministically constant or low DoFo of traditional task-specific AI systems), and there is a need to rethink our approach to RAI for general-purpose AI. Following this, we derive C2V2 (Control, Consistency, Value, Veracity) desiderata to meet the RAI requirements for future general-purpose AI systems, and discuss how recent efforts in AI alignment, retrieval-augmented generation, reasoning enhancements, etc. fare along one or more of the desiderata. We believe that the goal of developing responsible general-purpose AI can be achieved by formally modeling application- or domain-dependent RAI requirements along C2V2 dimensions, and taking a system design approach to suitably combine various techniques to meet the desiderata.
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DeepEvidence: Empowering Biomedical Discovery with Deep Knowledge Graph Research

arXiv:2601.11560v1 Announce Type: cross Abstract: Biomedical knowledge graphs (KGs) encode vast, heterogeneous information spanning literature, genes, pathways, drugs, diseases, and clinical trials, but leveraging them collectively for scientific discovery remains difficult. Their structural differences, continual evolution, and limited cross-resource alignment require substantial manual integration, limiting the depth and scale of knowledge exploration. We introduce DeepEvidence, an AI-agent framework designed to perform Deep Research across various heterogeneous biomedical KGs. Unlike generic Deep Research systems that rely primarily on internet-scale text, DeepEvidence incorporates specialized knowledge-graph tooling and coordinated exploration strategies to systematically bridge heterogeneous resources. At its core is an orchestrator that directs two complementary agents: Breadth-First ReSearch (BFRS) for broad, multi-graph entity search, and Depth-First ReSearch (DFRS) for multi-hop, evidence-focused reasoning. An internal, incrementally built evidence graph provides a structured record of retrieved entities, relations, and supporting evidence. To operate at scale, DeepEvidence includes unified interfaces for querying diverse biomedical APIs and an execution sandbox that enables programmatic data retrieval, extraction, and analysis. Across established deep-reasoning benchmarks and four key stages of the biomedical discovery lifecycle: drug discovery, pre-clinical experimentation, clinical trial development, and evidence-based medicine, DeepEvidence demonstrates substantial gains in systematic exploration and evidence synthesis. These results highlight the potential of knowledge-graph-driven Deep Research to accelerate biomedical discovery.
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Knowing When to Abstain: Medical LLMs Under Clinical Uncertainty

arXiv:2601.12471v1 Announce Type: cross Abstract: Current evaluation of large language models (LLMs) overwhelmingly prioritizes accuracy; however, in real-world and safety-critical applications, the ability to abstain when uncertain is equally vital for trustworthy deployment. We introduce MedAbstain, a unified benchmark and evaluation protocol for abstention in medical multiple-choice question answering (MCQA) -- a discrete-choice setting that generalizes to agentic action selection -- integrating conformal prediction, adversarial question perturbations, and explicit abstention options. Our systematic evaluation of both open- and closed-source LLMs reveals that even state-of-the-art, high-accuracy models often fail to abstain with uncertain. Notably, providing explicit abstention options consistently increases model uncertainty and safer abstention, far more than input perturbations, while scaling model size or advanced prompting brings little improvement. These findings highlight the central role of abstention mechanisms for trustworthy LLM deployment and offer practical guidance for improving safety in high-stakes applications.
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A Cloud-based Multi-Agentic Workflow for Science

arXiv:2601.12607v1 Announce Type: cross Abstract: As Large Language Models (LLMs) become ubiquitous across various scientific domains, their lack of ability to perform complex tasks like running simulations or to make complex decisions limits their utility. LLM-based agents bridge this gap due to their ability to call external resources and tools and thus are now rapidly gaining popularity. However, coming up with a workflow that can balance the models, cloud providers, and external resources is very challenging, making implementing an agentic system more of a hindrance than a help. In this work, we present a domain-agnostic, model-independent workflow for an agentic framework that can act as a scientific assistant while being run entirely on cloud. Built with a supervisor agent marshaling an array of agents with individual capabilities, our framework brings together straightforward tasks like literature review and data analysis with more complex ones like simulation runs. We describe the framework here in full, including a proof-of-concept system we built to accelerate the study of Catalysts, which is highly important in the field of Chemistry and Material Science. We report the cost to operate and use this framework, including the breakdown of the cost by services use. We also evaluate our system on a custom-curated synthetic benchmark and a popular Chemistry benchmark, and also perform expert validation of the system. The results show that our system is able to route the task to the correct agent 90% of the time and successfully complete the assigned task 97.5% of the time for the synthetic tasks and 91% of the time for real-world tasks, while still achieving better or comparable accuracy to most frontier models, showing that this is a viable framework for other scientific domains to replicate.
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SciHorizon-GENE: Benchmarking LLM for Life Sciences Inference from Gene Knowledge to Functional Understanding

arXiv:2601.12805v1 Announce Type: cross Abstract: Large language models (LLMs) have shown growing promise in biomedical research, particularly for knowledge-driven interpretation tasks. However, their ability to reliably reason from gene-level knowledge to functional understanding, However, their ability to reliably reason from gene-level knowledge to functional understanding, a core requirement for knowledge-enhanced cell atlas interpretation, remains largely underexplored. To address this gap, we introduce SciHorizon-GENE, a large-scale gene-centric benchmark constructed from authoritative biological databases. The benchmark integrates curated knowledge for over 190K human genes and comprises more than 540K questions covering diverse gene-to-function reasoning scenarios relevant to cell type annotation, functional interpretation, and mechanism-oriented analysis. Motivated by behavioral patterns observed in preliminary examinations, SciHorizon-GENE evaluates LLMs along four biologically critical perspectives: research attention sensitivity, hallucination tendency, answer completeness, and literature influence, explicitly targeting failure modes that limit the safe adoption of LLMs in biological interpretation pipelines. We systematically evaluate a wide range of state-of-the-art general-purpose and biomedical LLMs, revealing substantial heterogeneity in gene-level reasoning capabilities and persistent challenges in generating faithful, complete, and literature-grounded functional interpretations. Our benchmark establishes a systematic foundation for analyzing LLM behavior at the gene scale and offers insights for model selection and development, with direct relevance to knowledge-enhanced biological interpretation.
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