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Unlocking the Potential of Machine Learning and Large Language Models in Oncology – Pharmacy Times

A strength of using machine learning (ML) in oncology is its potential to extract data from unstructured documents, explained Will Shapiro, vice president of Data Science at Flatiron Health, during a session at the Association of Cancer Care Centers (ACCC) Annual Meeting & Cancer Center Business Summit (AMCCBS) in Washington DC. According to Shapiro, the ML team at Flatiron Health is focused on this endeavor in relation to oncology data and literature.

There's a ton of really rich information that's only in unstructured documents, Shapiro said during the session. We build models to extract things like metastatic status or diagnosis state, which are often not captured in any kind of regular structured way.

Image credit: ipopba | stock.adobe.com

Shapiro explained further that more recently, his ML team has started working with large language models (LLMs). He noted this space has significant potential within health care.

[At Flatiron Health] we built out a tool at the point of care that matches practice-authored regimens to NCCN guidelines, Shapiro said. That's something that we're really excited about.

Notably, Shapiro explained that his background is in fact not in health care, as he worked for many years at Spotify, where he built personalized recommendation engines using artificial intelligence (AI) and ML.

I really got excited about machine learning and AI in the context of building personalized recommendation engines [at Spotify], Shapiro explained. While personalizing music for a place like Spotify is radically different from personalizing medicine, I think there's actually some core things that really connect them, and I believe strongly that ML and AI have a key role to play in making truly personalized medicine a reality.

Shapiro noted that terminology can pose challenges for professionals in health care as they begin to dive into terms that contain a wealth of knowledge based on decades of research and thousands of dissertations. Terms such as LLM, natural language processing (NLP), generative AI, AI, and ML each represent an abundance of information that have helped us understand their potential today. Specifically, Shapiro noted that this collection of terms is distinct from workflow automation, which is another term in the same field that is often grouped together. Shapiro noted that workflow automation is distinct from these other terms in that currently there are well-known ways in which we evaluate quality for workflow automation.

With something like generative AIwhich is, I think, one of the most hyped things out in the world right nowit's so new that there really aren't ways that we can think about quality, Shapiro said. That's why I think it's really important to get educated and understand what's going on [around these terms].

According to Shapiro, a lot of these terms get used interchangeably, which can lead to additional confusion.

I think that there's a good reason for that, which is that there's a lot of overlap, Shapiro said. The same algorithm can be a deep learning algorithm and an NLP algorithm, and a lot of the applications are also the same.

Shapiro noted that one way of structuring these terms is to think of AI as a very broad category that encompasses ML, deep learning, and generative AI as nested subcategories. NLP, however, contains some differences.

There is an enormous amount of overlap between NLP and AI. A lot of the major advances in ML and AI stemmed from questions from NLP. But then there are also parts of NLP that are really distinct. [For example,] rules-based methods of parsing text are not something that I will think about with AI, and I will caveat this by saying that this is contentious, Shapiro said. If you google this, there will be 20 different ways that people try to structure this. My guidance is to not get too bogged down in the labels, but really try to focus on what the algorithm is or the product is that you're trying to understand.

According to Shapiro, one reason that oncologists should care about these terms is that ChatGPT, the most famous LLM currently in use today, is used by 1 in 10 doctors in their practice, according to a survey conducted over the summer of 2023. Shapiro noted that by the time of the presentation at the ACCC AMCCBS meeting in February 2024, that number has likely increased.

LLMs, which are large language models, are also a type of language model. According to Shapiro, the technical definition of a language model is a probability distribution over a sequence of words.

So, basically, given a chunk of text, what is the probability that any word will follow the chunk that you're looking at, Shapiro said. LLMs are essentially language models that are trained on the internet, so they're enormous.

According to Shapiro, language models can also be used to generate text. For instance, in the example My best friend and I are so close, we finish each other's ___ it is not difficult for humans to finish this with the appropriate word in the blank, which in this case would be sentences. Shapiro explained that is very much how language models work.

Probabilistically, sentence is the missing word [in that example], which is very much at the core of what's happening with a language model, Shapiro said. In fact, autocomplete, which you probably don't even think about as you see it every day, is generative AI that's an example [of a language model], and it's one of the motivating examples of generative AI.

To be clear in terms of definition, Shapiro noted that generative AI are AI models that generate new content. Specifically, the GPT in ChatGPT (which is both an LLM and generative AI) stands for generative pre-trained transformer. According to Shapiro, pre-trained models can be understood as having a foundational knowledge, which is in contrast to other kinds of models that just do one task.

I mentioned my team works on building models that will extract metastatic status from documents, and that's all they do, Shapiro said. In contrast, pre-trained models can do a lot of different kinds of things. They can classify the sentiment of reviews, they can flag abusive messages, and they probably are going to write the next 10 Harry Potter novels. They can extract adverse events from charts, and they can also do things that extract metastatic status. So, that's a big part of the appealone model can do a lot of different things.

However, this capacity of one model being capable of doing many different things can also have a trade off in terms of quality. Shapiro explained that that is something his team at Flatiron Health has found to be true in their work.

What we've found at Flatiron Health is that generally, purpose-built models can be much better at actually predicting or doing one task. But one thing that's become really exciting, and kind of gets into the weeds of LLMs, is this concept of taking a pre-trained model and fine-tuning it on labeled examples, which is a way to really increase the performance of a pre-trained model.

Further, the T in ChatGPT stands for transformer, which is a type of deep learning architecture that was developed at Google in 2017, explained Shapiro. It was originally described in a paper called Attention is All You Need.

Transformers are actually kind of simple, Shapiro said. If you read about the history of deep learning, model architectures tended to get more and more complex, and the transformer actually stripped away a fair amount of this complexity. But what's been really game changing is how big they are, as they're trained on the internet. So things like Wikipedia, Redditthese huge corpuses of texthave billions of grammars, and they're really, really expensive to train.

Yet, the size of them is what has led to these incredible breakthroughs in performance and benchmarks that have caused quite a bit of buzz recently, explained Shapiro. With this buzz and attention raises the importance of becoming more educated in what these models are and how they work, especially in areas such as health care.

With 10% of doctors using ChatGPT, it is something that everyone really needs to get educated about pretty quickly. I also just think there are so many exciting ways that ML and AI have a role to play in the future of oncology, Shapiro said.

Shapiro explained further that using these models, there is the potential in oncology to conduct research that is pulled from enormous patient populations, which can made available at scale. Additionally, there is the potential to summarize visit notes from audio recordings, to predict patient response to a treatment, and to discover new drug targets.

There are huge opportunities in ML and AI, but there are also a lot of challenges and a lot of open questions. When you see someone like Sam Altman, the CEO of OpenAI, going to Congress and asking it to be regulated, you know that there's something to pay attention to, Shapiro said. That's because there's some real problems.

Such problems include hallucinations, which consists of models inventing answers. Shapiro explained what makes hallucinations by AI models even more pernicious is that they come from a place of technological authority.

There's an inherent inclination to trust them, Shapiro said. There's a lot of traditional considerations for any type of ML or AI algorithm around whether they are biased, whether they are perpetuating inequity, and whether data shifts affect their quality. For this reason, I think it's more important than ever to really think closely about how you're validating the quality of models. High quality ground truth data, I think, is essential for using any of these types of ML or AI algorithms.

Reference

Shapiro W. Deep Dive 6. Artificial and Business Intelligence Technology. Presented at: ACCC AMCCBS; February 28-March 1, 2024; Washington, DC.

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Unlocking the Potential of Machine Learning and Large Language Models in Oncology - Pharmacy Times

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To find rare frogs and birds, Pitt researchers are using machine learning algorithms and hundreds of microphones – University of Pittsburgh

It used to be that if you wanted to track down a rare frog, youd have to go to a likely place and wait until you heard its call. The rarer the frog, the less likely it was youd hear one.

Now, there are better tools for that.

The technologies that we work with are designed mostly to give you a better chance of detecting things that are hard to detect, said Justin Kitzes, an assistant professor of biological sciences in the Kenneth P. Dietrich School of Arts and Sciences.

Kitzes makes use of tools for bioacoustics the study of sounds made by animals which, along with satellite imaging and DNA methods, is part of a new generation of conservation technologies that allow researchers to search more broadly and efficiently than ever before.

At the beginning of a project, researchers in his lab place up to hundreds of sensors that listen in on an area of interest. Then researchers bring those recordings into the lab, where they sort the signal from the noise. And theres plenty of noise.

Each recorder can track about 150 hours of sound, and when the team deploys 50 sensors, as they did recently when searching for frogs in Panama, those hours add up.

7,500 is pretty small for us, because 50 recorders is actually a small deployment, Kitzes said. In our bird work, its more like 75,000 hours.

Theres no use in collecting eight continuous years of audio if you dont have time to listen to it, though. The labs research owes thanks to two technologies made available in 2017: an inexpensive audio recorder that allows the team to deploy hundreds of sensors and an open-source platform that gave scientists the ability to develop machine learning tools to sort through the data.

That was really what kicked everything off, said Kitzes. Because that gave us an explosion of field data along with the ability to train deep learning models to analyze it.

Tracking birds using this technology is one main focus for the team.

Another is its amphibian research, a collaboration with the lab of Biological Sciences Professor Corinne Richards-Zawacki as part of the RIBBITR program. That work, including biological sciences graduate student Sam Lapp and staff researcher Alexandra Syunkova, has the team focusing on sites in Pennsylvania, California, Panama and Brazil.

In one recent instance, audio recordings helped the researchers track down an elusive variable harlequin toad (pictured above) in an unlikely site in Panama that was only just beginning to recover from an outbreak of the deadly chytrid fungus. And just this year, the team published a study led by Lapp where they listened in on the underwater behavior of the endangered Sierra Nevada yellow-legged frog.

Studies like the latter rely on training what's called convolutional neural network models related to the ones used by tech companies use to recognize features in photos to categorize different types of sounds when presented with a visual representation of the audio recordings.

Were using the same kinds of models as Google and Amazon, where in your vacation photo albums they might be able to recognize a palm tree by a beach, Kitzes said.

But as high-tech as the work is, theres no replacement for the eye of a trained human. Members of the lab always check some of the algorithms work to ensure that its looking for the right calls. Its similar, Kitzes explains, to how he sees other uses of machine learning and artificial intelligence: Not as a replacement for the work of humans, but as a way to augment it.

"The reason our lab exists is that were trying to make conservation biologists and ecologists more effective at their job, said Kitzes. So they can get out there, find more species, learn better about whats impacting those species and, ultimately, take the actions that are necessary to conserve those species and protect biodiversity.

Patrick Monahan, photography by Corinne Richards-Zawacki

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To find rare frogs and birds, Pitt researchers are using machine learning algorithms and hundreds of microphones - University of Pittsburgh

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Seeing Our Reflection in LLMs. When LLMs give us outputs that reveal | by Stephanie Kirmer | Mar, 2024 – Towards Data Science

Photo by Vince Fleming on Unsplash

By now, Im sure most of you have heard the news about Googles new LLM*, Gemini, generating pictures of racially diverse people in Nazi uniforms. This little news blip reminded me of something that Ive been meaning to discuss, which is when models have blind spots, so we apply expert rules to the predictions they generate to avoid returning something wildly outlandish to the user.

This sort of thing is not that uncommon in machine learning, in my experience, especially when you have flawed or limited training data. A good example of this that I remember from my own work was predicting when a package was going to be delivered to a business office. Mathematically, our model would be very good at estimating exactly when the package would get physically near the office, but sometimes, truck drivers arrive at destinations late at night and then rest in their truck or in a hotel until morning. Why? Because no ones in the office to receive/sign for the package outside of business hours.

Teaching a model about the idea of business hours can be very difficult, and the much easier solution was just to say, If the model says the delivery will arrive outside business hours, add enough time to the prediction that it changes to the next hour the office is listed as open. Simple! It solves the problem and it reflects the actual circumstances on the ground. Were just giving the model a little boost to help its results work better.

However, this does cause some issues. For one thing, now we have two different model predictions to manage. We cant just throw away the original model prediction, because thats what we use for model performance monitoring and metrics. You cant assess a model on predictions after humans got their paws in there, thats not mathematically sound. But to get a clear sense of the real world model impact, you do want to look at the post-rule prediction, because thats what the customer actually experienced/saw in your application. In ML, were used to a very simple framing, where every time you run a model you get one result or set of results, and thats that, but when you start tweaking the results before you let them go, then you need to think at a different scale.

I kind of suspect that this is a form of whats going on with LLMs like Gemini. However, instead of a post-prediction rule, it appears that the smart money says Gemini and other models are applying secret prompt augmentations to try and change the results the LLMs produce.

In essence, without this nudging, the model will produce results that are reflective of the content it has been trained on. That is to say, the content produced by real people. Our social media posts, our history books, our museum paintings, our popular songs, our Hollywood movies, etc. The model takes in all that stuff, and it learns the underlying patterns in it, whether they are things were proud of or not. A model given all the media available in our contemporary society is going to get a whole lot of exposure to racism, sexism, and myriad other forms of discrimination and inequality, to say nothing of violence, war, and other horrors. While the model is learning what people look like, and how they sound, and what they say, and how they move, its learning the warts-and-all version.

Our social media posts, our history books, our museum paintings, our popular songs, our Hollywood movies, etc. The model takes in all that stuff, and it learns the underlying patterns in it, whether they are things were proud of or not.

This means that if you ask the underlying model to show you a doctor, its going to probably be a white guy in a lab coat. This isnt just random, its because in our modern society white men have disproportionate access to high status professions like being doctors, because they on average have access to more and better education, financial resources, mentorship, social privilege, and so on. The model is reflecting back at us an image that may make us uncomfortable because we dont like to think about that reality.

The obvious argument is, Well, we dont want the model to reinforce the biases our society already has, we want it to improve representation of underrepresented populations. I sympathize with this argument, quite a lot, and I care about representation in our media. However, theres a problem.

Its very unlikely that applying these tweaks is going to be a sustainable solution. Recall back to the story I started with about Gemini. Its like playing whac-a-mole, because the work never stops now weve got people of color being shown in Nazi uniforms, and this is understandably deeply offensive to lots of folks. So, maybe where we started by randomly applying as a black person or as an indigenous person to our prompts, we have to add something more to make it exclude cases where its inappropriate but how do you phrase that, in a way an LLM can understand? We probably have to go back to the beginning, and think about how the original fix works, and revisit the whole approach. In the best case, applying a tweak like this fixes one narrow issue with outputs, while potentially creating more.

Lets play out another very real example. What if we add to the prompt, Never use explicit or profane language in your replies, including [list of bad words here]. Maybe that works for a lot of cases, and the model will refuse to say bad words that a 13 year old boy is requesting to be funny. But sooner or later, this has unexpected additional side effects. What about if someones looking for the history of Sussex, England? Alternately, someones going to come up with a bad word you left out of the list, so thats going to be constant work to maintain. What about bad words in other languages? Who judges what goes on the list? I have a headache just thinking about it.

This is just two examples, and Im sure you can think of more such scenarios. Its like putting band aid patches on a leaky pipe, and every time you patch one spot another leak springs up.

So, what is it we actually want from LLMs? Do we want them to generate a highly realistic mirror image of what human beings are actually like and how our human society actually looks from the perspective of our media? Or do we want a sanitized version that cleans up the edges?

Honestly, I think we probably need something in the middle, and we have to continue to renegotiate the boundaries, even though its hard. We dont want LLMs to reflect the real horrors and sewers of violence, hate, and more that human society contains, that is a part of our world that should not be amplified even slightly. Zero content moderation is not the answer. Fortunately, this motivation aligns with the desires of large corporate entities running these models to be popular with the public and make lots of money.

we have to continue to renegotiate the boundaries, even though its hard. We dont want LLMs to reflect the real horrors and sewers of violence, hate, and more that human society contains, that is a part of our world that should not be amplified even slightly. Zero content moderation is not the answer.

However, I do want to continue to make a gentle case for the fact that we can also learn something from this dilemma in the world of LLMs. Instead of simply being offended and blaming the technology when a model generates a bunch of pictures of a white male doctor, we should pause to understand why thats what we received from the model. And then we should debate thoughtfully about whether the response from the model should be allowed, and make a decision that is founded in our values and principles, and try to carry it out to the best of our ability.

As Ive said before, an LLM isnt an alien from another universe, its us. Its trained on the things we wrote/said/filmed/recorded/did. If we want our model to show us doctors of various sexes, genders, races, etc, we need to make a society that enables all those different kinds of people to have access to that profession and the education it requires. If were worrying about how the model mirrors us, but not taking to heart the fact that its us that needs to be better, not just the model, then were missing the point.

If we want our model to show us doctors of various sexes, genders, races, etc, we need to make a society that enables all those different kinds of people to have access to that profession and the education it requires.

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Seeing Our Reflection in LLMs. When LLMs give us outputs that reveal | by Stephanie Kirmer | Mar, 2024 - Towards Data Science

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Generative artificial intelligence: synthetic datasets in dentistry | BDJ Open – Nature.com

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UTSW team’s new AI method may lead to ‘automated scientists’ – UT Southwestern

Deep distilling is an automated method that learns relationships in data using essence neural networks. It then condenses the neural representation of these relationships into human-understandable rules, usually in the form of executable computer code that is much more concise than the neural network. (Illustration credit: Anda Kim)

DALLAS Feb. 29, 2024 UTSouthwestern Medical Center researchers have developed an artificial intelligence (AI) method that writes its own algorithms and may one day operate as an automated scientist to extract the meaning behind complex datasets.

Milo Lin, Ph.D., is Assistant Professor in the Lyda Hill Department of Bioinformatics, Biophysics, and the Center for Alzheimer's and Neurodegenerative Diseases at UTSouthwestern.

Researchers are increasingly employing AI and machine learning models in their work, but with the huge caveat that these high-performing models provide limited new direct insights into the data, saidMilo Lin, Ph.D., Assistant Professor intheLyda Hill Department of Bioinformatics,Biophysics,and theCenter for Alzheimers and Neurodegenerative Diseasesat UTSouthwestern.Our work is the first step in allowing researchers to use AI to directly convert complex data into new human-understandable insights.

Dr. Lin co-led the study, published inNature Computational Science,with first author Paul J. Blazek, M.D., Ph.D.,who worked on this project as part of his thesis work while he was at UTSW.

In the past several years, the field of AI has seen enormous growth, with significant crossover from basic and applied scientific discovery to popular use. One commonly used branch of AI, known as neural networks, emulates the structure of the human brain by mimicking the way biological neurons signal one another. Neural networks are a form of machine learning, which creates outputs based on input data after learning on a training dataset.

Although this tool has found significant use in applications such as image and speech recognition, conventional neural networks have significant drawbacks, Dr. Lin said. Most notably, they often dont generalizefarbeyond the data they train on, and the rationale for their output is a black box, meaning theres no way for researchers to understand how a neural network algorithm reached its conclusion.This study was supported by UTSWs High Impact Grant Program, which was initiated in 2001 and supports high-risk research offering high potential impact in basic science or medicine.

Seeking to address both issues, the UTSW researchers developed a method they call deep distilling. Using limited training data datasets used to train machine learning models deep distilling automatically discovers algorithms, or the rules to explain observed input-output patterns in the data. This is done by training an essence neural network (ENN), previously developed in the Lin Lab, on input-output data. The parameters of the ENN that encode the learned algorithm are then translated into succinct computer codes so users can read them.

The researchers tested deep distilling in a variety of scenarios in which traditional neural networks cannot produce human-comprehensible rules and have poor performance in generalizing to very different data. These included cellular automata, in which grids contain hypothetical cells in distinct states that evolve over time according to a set of rules often used as model systems for emergent behavior in the physical, life, and computer sciences. Although the grid used by the researchers had 256 possible sets of rules, deep distilling was able to learn the rules for accurately predicting the hypothetical cells behavior for every set of rules after seeing only grids from 16 rule sets, summarizing all 256 rule sets in a single algorithm.

In another test, the researchers trained deep distilling to accurately classify a shapes orientation as vertical or horizontal. Although only a few training images of perfectly horizontal or vertical lines were required, this method was able to apply the succinct algorithm it discovered to accurately solve much more ambiguous cases, such as patterns with multiple lines or gradients and shapes made of boxes as well as zigzag, diagonal, or dotted lines.

Eventually, Dr. Lin said, deep distilling could be applied to the vast datasets generated by high-throughput scientific studies, such as those used for drug discovery, and act as an automated scientist capturing patterns in results not easily discernible to the human brain, such as how DNA sequences encode functional rules of biomolecular interactions. Deep distilling also could potentially serve as a decision-making aid to doctors, offering insights on its thought process through the generated algorithms, he added.

This study was supported by UTSWs High Impact Grant Program, which was initiated in 2001 and supports high-risk research offering high potential impact in basic science or medicine.

About UTSouthwestern Medical Center

UTSouthwestern, one of the nations premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institutions faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UTSouthwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

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Using machine learning to identify key predictors of mortality in dementia patients – News-Medical.Net

Researchers at the Icahn School of Medicine at Mount Sinai and others have harnessed the power of machine learning to identify key predictors of mortality in dementia patients.

The study, published in the February 28 online issue of Communications Medicine [10.1038/s43856-024-00437-7], addresses critical challenges in dementia care by pinpointing patients at high risk of near-term death and uncovers the factors that drive this risk. Unlike previous studies that focused on diagnosing dementia, this research delves into predicting patient prognosis, shedding light on mortality risks and contributing factors in various kinds of dementia.

Dementia has emerged as a major cause of death in societies with increasingly aging populations. However, predicting the exact timing of death in dementia cases is challenging due to the variable progression of cognitive decline affecting the body's normal functions, say the researchers.

Our findings are significant as they illustrate the potential of machine learning models to accurately anticipate mortality risk in dementia patients over varying timeframes. By pinpointing a concise set of clinical features, including performance on neuropsychological and other available testing, our models empower health care providers to make more informed decisions about patient care, potentially leading to more tailored and timely interventions."

Kuan-lin Huang, PhD, Corresponding Author, Assistant Professor of Genetics and Genomic Sciences at Icahn Mount Sinai

Using data from the U.S. National Alzheimer's Coordinating Center that included 45,275 participants and 163,782 visit records, the study created machine learning models based on clinical and neurocognitive features. These models predicted mortality at one, three, five, and 10 years. The study developed specific models for eight types of dementia through stratified analyses.

The study also found that neuropsychological test results were a better predictor of mortality risk in dementia patients than age-related factors such as cancer and heart disease, underscoring dementia's significant role in mortality among those with neurodegenerative conditions.

"The implications of our research extend beyond clinical practice, as it underscores the value of machine learning in unraveling the complexities of diseases like dementia. This study lays the groundwork for future investigations into predictive modeling in dementia care," says Dr. Huang. "However, while machine learning holds great promise for improving dementia care, it's important to remember that these models aren't crystal balls for individual outcomes. Many factors, both personal and medical, shape a patient's journey."

Next, the research team plans to refine their models by incorporating treatment effects and genetic data and exploring advanced deep-learning techniques for even more precise predictions.

Given the aging population, dementia has emerged as an increasingly pressing public health concern, ranking as the seventh leading cause of death and the fourth most burdensome disease or injury in the United States in 2016, based on years of life lost. As of 2022, Alzheimer's and other dementias cost an estimated $1 trillion annually, impacting approximately 6.5 million Americans and 57.4 million people worldwide, with projections suggesting a tripling by 2050.

The paper is titled "Machine learning models identify predictive features of patient mortality across dementia types."

The remaining authors on the paper are Jimmy Zhang (currently at Columbia University); Luo Song (currently an MD candidate at The University of Queensland, Australia); Zachary Miller (University of Washington, Seattle); and Kwun C. G. Chan, PhD (University of Washington, Seattle).

Source:

Journal reference:

Zhang, J., et al. (2024). Machine learning models identify predictive features of patient mortality across dementia types.Communications Medicine. doi.org/10.1038/s43856-024-00437-7.

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Using machine learning to identify key predictors of mortality in dementia patients - News-Medical.Net

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