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One of the hardest parts of writing a research paper can be just finding a good topic to write about. Fortunately we've done the hard work for you and have compiled a list of 113 interesting research paper topics. They've been organized into ten categories and cover a wide range of subjects so you can easily find the best topic for you.

In addition to the list of good research topics, we've included advice on what makes a good research paper topic and how you can use your topic to start writing a great paper.

What Makes a Good Research Paper Topic?

Not all research paper topics are created equal, and you want to make sure you choose a great topic before you start writing. Below are the three most important factors to consider to make sure you choose the best research paper topics.

#1: It's Something You're Interested In

A paper is always easier to write if you're interested in the topic, and you'll be more motivated to do in-depth research and write a paper that really covers the entire subject. Even if a certain research paper topic is getting a lot of buzz right now or other people seem interested in writing about it, don't feel tempted to make it your topic unless you genuinely have some sort of interest in it as well.

#2: There's Enough Information to Write a Paper

Even if you come up with the absolute best research paper topic and you're so excited to write about it, you won't be able to produce a good paper if there isn't enough research about the topic. This can happen for very specific or specialized topics, as well as topics that are too new to have enough research done on them at the moment. Easy research paper topics will always be topics with enough information to write a full-length paper.

Trying to write a research paper on a topic that doesn't have much research on it is incredibly hard, so before you decide on a topic, do a bit of preliminary searching and make sure you'll have all the information you need to write your paper.

#3: It Fits Your Teacher's Guidelines

Don't get so carried away looking at lists of research paper topics that you forget any requirements or restrictions your teacher may have put on research topic ideas. If you're writing a research paper on a health-related topic, deciding to write about the impact of rap on the music scene probably won't be allowed, but there may be some sort of leeway. For example, if you're really interested in current events but your teacher wants you to write a research paper on a history topic, you may be able to choose a topic that fits both categories, like exploring the relationship between the US and North Korea. No matter what, always get your research paper topic approved by your teacher first before you begin writing.

113 Good Research Paper Topics

Below are 113 good research topics to help you get you started on your paper. We've organized them into ten categories to make it easier to find the type of research paper topics you're looking for.

Arts/Culture

• Discuss the main differences in art from the Italian Renaissance and the Northern Renaissance .
• Analyze the impact a famous artist had on the world.
• How is sexism portrayed in different types of media (music, film, video games, etc.)? Has the amount/type of sexism changed over the years?
• How has the music of slaves brought over from Africa shaped modern American music?
• How has rap music evolved in the past decade?
• How has the portrayal of minorities in the media changed?

Current Events

• What have been the impacts of China's one child policy?
• How have the goals of feminists changed over the decades?
• How has the Trump presidency changed international relations?
• Analyze the history of the relationship between the United States and North Korea.
• What factors contributed to the current decline in the rate of unemployment?
• What have been the impacts of states which have increased their minimum wage?
• How do US immigration laws compare to immigration laws of other countries?
• How have the US's immigration laws changed in the past few years/decades?
• How has the Black Lives Matter movement affected discussions and view about racism in the US?
• What impact has the Affordable Care Act had on healthcare in the US?
• What factors contributed to the UK deciding to leave the EU (Brexit)?
• What factors contributed to China becoming an economic power?
• Discuss the history of Bitcoin or other cryptocurrencies  (some of which tokenize the S&P 500 Index on the blockchain) .
• Do students in schools that eliminate grades do better in college and their careers?
• Do students from wealthier backgrounds score higher on standardized tests?
• Do students who receive free meals at school get higher grades compared to when they weren't receiving a free meal?
• Do students who attend charter schools score higher on standardized tests than students in public schools?
• Do students learn better in same-sex classrooms?
• How does giving each student access to an iPad or laptop affect their studies?
• What are the benefits and drawbacks of the Montessori Method ?
• Do children who attend preschool do better in school later on?
• What was the impact of the No Child Left Behind act?
• How does the US education system compare to education systems in other countries?
• What impact does mandatory physical education classes have on students' health?
• Which methods are most effective at reducing bullying in schools?
• Do homeschoolers who attend college do as well as students who attended traditional schools?
• Does offering tenure increase or decrease quality of teaching?
• How does college debt affect future life choices of students?
• Should graduate students be able to form unions?

• What are different ways to lower gun-related deaths in the US?
• How and why have divorce rates changed over time?
• Is affirmative action still necessary in education and/or the workplace?
• Should physician-assisted suicide be legal?
• How has stem cell research impacted the medical field?
• How can human trafficking be reduced in the United States/world?
• Should people be able to donate organs in exchange for money?
• Which types of juvenile punishment have proven most effective at preventing future crimes?
• Has the increase in US airport security made passengers safer?
• Analyze the immigration policies of certain countries and how they are similar and different from one another.
• Several states have legalized recreational marijuana. What positive and negative impacts have they experienced as a result?
• Do tariffs increase the number of domestic jobs?
• Which prison reforms have proven most effective?
• Should governments be able to censor certain information on the internet?
• Which methods/programs have been most effective at reducing teen pregnancy?
• What are the benefits and drawbacks of the Keto diet?
• How effective are different exercise regimes for losing weight and maintaining weight loss?
• How do the healthcare plans of various countries differ from each other?
• What are the most effective ways to treat depression ?
• What are the pros and cons of genetically modified foods?
• Which methods are most effective for improving memory?
• What can be done to lower healthcare costs in the US?
• What factors contributed to the current opioid crisis?
• Analyze the history and impact of the HIV/AIDS epidemic .
• Are low-carbohydrate or low-fat diets more effective for weight loss?
• How much exercise should the average adult be getting each week?
• Which methods are most effective to get parents to vaccinate their children?
• What are the pros and cons of clean needle programs?
• How does stress affect the body?
• Discuss the history of the conflict between Israel and the Palestinians.
• What were the causes and effects of the Salem Witch Trials?
• Who was responsible for the Iran-Contra situation?
• How has New Orleans and the government's response to natural disasters changed since Hurricane Katrina?
• What events led to the fall of the Roman Empire?
• What were the impacts of British rule in India ?
• Was the atomic bombing of Hiroshima and Nagasaki necessary?
• What were the successes and failures of the women's suffrage movement in the United States?
• What were the causes of the Civil War?
• How did Abraham Lincoln's assassination impact the country and reconstruction after the Civil War?
• Which factors contributed to the colonies winning the American Revolution?
• What caused Hitler's rise to power?
• Discuss how a specific invention impacted history.
• What led to Cleopatra's fall as ruler of Egypt?
• How has Japan changed and evolved over the centuries?
• What were the causes of the Rwandan genocide ?

• Why did Martin Luther decide to split with the Catholic Church?
• Analyze the history and impact of a well-known cult (Jonestown, Manson family, etc.)
• How did the sexual abuse scandal impact how people view the Catholic Church?
• How has the Catholic church's power changed over the past decades/centuries?
• What are the causes behind the rise in atheism/ agnosticism in the United States?
• What were the influences in Siddhartha's life resulted in him becoming the Buddha?
• How has media portrayal of Islam/Muslims changed since September 11th?

Science/Environment

• How has the earth's climate changed in the past few decades?
• How has the use and elimination of DDT affected bird populations in the US?
• Analyze how the number and severity of natural disasters have increased in the past few decades.
• Analyze deforestation rates in a certain area or globally over a period of time.
• How have past oil spills changed regulations and cleanup methods?
• How has the Flint water crisis changed water regulation safety?
• What are the pros and cons of fracking?
• What impact has the Paris Climate Agreement had so far?
• What have NASA's biggest successes and failures been?
• How can we improve access to clean water around the world?
• Does ecotourism actually have a positive impact on the environment?
• Should the US rely on nuclear energy more?
• What can be done to save amphibian species currently at risk of extinction?
• What impact has climate change had on coral reefs?
• How are black holes created?
• Are teens who spend more time on social media more likely to suffer anxiety and/or depression?
• How will the loss of net neutrality affect internet users?
• Analyze the history and progress of self-driving vehicles.
• How has the use of drones changed surveillance and warfare methods?
• Has social media made people more or less connected?
• What progress has currently been made with artificial intelligence ?
• Do smartphones increase or decrease workplace productivity?
• What are the most effective ways to use technology in the classroom?
• How is Google search affecting our intelligence?
• When is the best age for a child to begin owning a smartphone?
• Has frequent texting reduced teen literacy rates?

How to Write a Great Research Paper

Even great research paper topics won't give you a great research paper if you don't hone your topic before and during the writing process. Follow these three tips to turn good research paper topics into great papers.

#1: Figure Out Your Thesis Early

Before you start writing a single word of your paper, you first need to know what your thesis will be. Your thesis is a statement that explains what you intend to prove/show in your paper. Every sentence in your research paper will relate back to your thesis, so you don't want to start writing without it!

As some examples, if you're writing a research paper on if students learn better in same-sex classrooms, your thesis might be "Research has shown that elementary-age students in same-sex classrooms score higher on standardized tests and report feeling more comfortable in the classroom."

If you're writing a paper on the causes of the Civil War, your thesis might be "While the dispute between the North and South over slavery is the most well-known cause of the Civil War, other key causes include differences in the economies of the North and South, states' rights, and territorial expansion."

#2: Back Every Statement Up With Research

Remember, this is a research paper you're writing, so you'll need to use lots of research to make your points. Every statement you give must be backed up with research, properly cited the way your teacher requested. You're allowed to include opinions of your own, but they must also be supported by the research you give.

#3: Do Your Research Before You Begin Writing

You don't want to start writing your research paper and then learn that there isn't enough research to back up the points you're making, or, even worse, that the research contradicts the points you're trying to make!

Get most of your research on your good research topics done before you begin writing. Then use the research you've collected to create a rough outline of what your paper will cover and the key points you're going to make. This will help keep your paper clear and organized, and it'll ensure you have enough research to produce a strong paper.

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Christine graduated from Michigan State University with degrees in Environmental Biology and Geography and received her Master's from Duke University. In high school she scored in the 99th percentile on the SAT and was named a National Merit Finalist. She has taught English and biology in several countries.

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1000+ FREE Research Topics & Ideas

If you’re at the start of your research journey and are trying to figure out which research topic you want to focus on, you’ve come to the right place. Select your area of interest below to view a comprehensive collection of potential research ideas.

Research Topic FAQs

What (exactly) is a research topic.

A research topic is the subject of a research project or study – for example, a dissertation or thesis. A research topic typically takes the form of a problem to be solved, or a question to be answered.

A good research topic should be specific enough to allow for focused research and analysis. For example, if you are interested in studying the effects of climate change on agriculture, your research topic could focus on how rising temperatures have impacted crop yields in certain regions over time.

To learn more about the basics of developing a research topic, consider our free research topic ideation webinar.

What constitutes a good research topic?

A strong research topic comprises three important qualities : originality, value and feasibility.

• Originality – a good topic explores an original area or takes a novel angle on an existing area of study.
• Value – a strong research topic provides value and makes a contribution, either academically or practically.
• Feasibility – a good research topic needs to be practical and manageable, given the resource constraints you face.

To learn more about what makes for a high-quality research topic, check out this post .

What's the difference between a research topic and research problem?

A research topic and a research problem are two distinct concepts that are often confused. A research topic is a broader label that indicates the focus of the study , while a research problem is an issue or gap in knowledge within the broader field that needs to be addressed.

To illustrate this distinction, consider a student who has chosen “teenage pregnancy in the United Kingdom” as their research topic. This research topic could encompass any number of issues related to teenage pregnancy such as causes, prevention strategies, health outcomes for mothers and babies, etc.

Within this broad category (the research topic) lies potential areas of inquiry that can be explored further – these become the research problems . For example:

• What factors contribute to higher rates of teenage pregnancy in certain communities?
• How do different types of parenting styles affect teen pregnancy rates?
• What interventions have been successful in reducing teenage pregnancies?

Simply put, a key difference between a research topic and a research problem is scope ; the research topic provides an umbrella under which multiple questions can be asked, while the research problem focuses on one specific question or set of questions within that larger context.

How can I find potential research topics for my project?

There are many steps involved in the process of finding and choosing a high-quality research topic for a dissertation or thesis. We cover these steps in detail in this video (also accessible below).

How can I find quality sources for my research topic?

Finding quality sources is an essential step in the topic ideation process. To do this, you should start by researching scholarly journals, books, and other academic publications related to your topic. These sources can provide reliable information on a wide range of topics. Additionally, they may contain data or statistics that can help support your argument or conclusions.

Identifying Relevant Sources

When searching for relevant sources, it’s important to look beyond just published material; try using online databases such as Google Scholar or JSTOR to find articles from reputable journals that have been peer-reviewed by experts in the field.

You can also use search engines like Google or Bing to locate websites with useful information about your topic. However, be sure to evaluate any website before citing it as a source—look for evidence of authorship (such as an “About Us” page) and make sure the content is up-to-date and accurate before relying on it.

Evaluating Sources

Once you’ve identified potential sources for your research project, take some time to evaluate them thoroughly before deciding which ones will best serve your purpose. Consider factors such as author credibility (are they an expert in their field?), publication date (is the source current?), objectivity (does the author present both sides of an issue?) and relevance (how closely does this source relate to my specific topic?).

By researching the current literature on your topic, you can identify potential sources that will help to provide quality information. Once you’ve identified these sources, it’s time to look for a gap in the research and determine what new knowledge could be gained from further study.

How can I find a good research gap?

Finding a strong gap in the literature is an essential step when looking for potential research topics. We explain what research gaps are and how to find them in this post.

How should I evaluate potential research topics/ideas?

When evaluating potential research topics, it is important to consider the factors that make for a strong topic (we discussed these earlier). Specifically:

• Originality
• Feasibility

So, when you have a list of potential topics or ideas, assess each of them in terms of these three criteria. A good topic should take a unique angle, provide value (either to academia or practitioners), and be practical enough for you to pull off, given your limited resources.

Finally, you should also assess whether this project could lead to potential career opportunities such as internships or job offers down the line. Make sure that you are researching something that is relevant enough so that it can benefit your professional development in some way. Additionally, consider how each research topic aligns with your career goals and interests; researching something that you are passionate about can help keep motivation high throughout the process.

How can I assess the feasibility of a research topic?

When evaluating the feasibility and practicality of a research topic, it is important to consider several factors.

First, you should assess whether or not the research topic is within your area of competence. Of course, when you start out, you are not expected to be the world’s leading expert, but do should at least have some foundational knowledge.

Time commitment

When considering a research topic, you should think about how much time will be required for completion. Depending on your field of study, some topics may require more time than others due to their complexity or scope.

Additionally, if you plan on collaborating with other researchers or institutions in order to complete your project, additional considerations must be taken into account such as coordinating schedules and ensuring that all parties involved have adequate resources available.

Resources needed

It’s also critically important to consider what type of resources are necessary in order to conduct the research successfully. This includes physical materials such as lab equipment and chemicals but can also include intangible items like access to certain databases or software programs which may be necessary depending on the nature of your work. Additionally, if there are costs associated with obtaining these materials then this must also be factored into your evaluation process.

Potential risks

It’s important to consider the inherent potential risks for each potential research topic. These can include ethical risks (challenges getting ethical approval), data risks (not being able to access the data you’ll need), technical risks relating to the equipment you’ll use and funding risks (not securing the necessary financial back to undertake the research).

If you’re looking for more information about how to find, evaluate and select research topics for your dissertation or thesis, check out our free webinar here . Alternatively, if you’d like 1:1 help with the topic ideation process, consider our private coaching services .

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500 Good Research Paper Topics

Bonus Material: Essential essay checklist

Writing a research paper for a class and not sure how to start?

One of the most important steps to creating a great paper is finding a good topic! 

Here’s a hand-drafted list from a Princeton grad who has helped professors at Harvard and Yale edit their papers for publication and taught college writing at the University of Notre Dame and .

What’s more, we give you some foolproof formulas for creating your own paper topic to fit the requirements of your class.

Using these simple formulas, we’ve helped hundreds of students turn a B- paper topic into an A+ paper topic.

Keep reading for our list of 500 vetted research paper topics and our magic formulas for creating your own topic!

Of course, if you want help learning to write research papers tailored to your individual needs, check out our one-on-one writing coaching or academic writing workshop . Set up a free consultation to see how we can help you learn to write A+ papers!

Jump to paper topics in:

European & Mediterranean History

African history, asian history, history of the pre-columbian americas.

• Latin American History

History of Science

Politics & public policy, education & education policy, political theory, science policy.

• Health Sciences & Psychology

What is a research paper?

In order to write a good research paper, it’s important to know what it is! 

In general, we can divide academic writing into three broad categories:

• Analytical: analyze the tools an author uses to make their point
• Research: delve deeply into a research topic and share your findings
• Persuasive : argue a specific and nuanced position backed by evidence

What’s the difference between an analytical paper and a research paper? For an analytical paper, it’s okay to just use one or two sources (a book, poem, work of art, piece of music, etc.) and examine them in detail. For a research paper, however, the expectation is that you do, well . . . research .

The depth of research that you’re expected to do will depend on your age and the type of class you’re taking.

In elementary or middle school, a “research paper” might mean finding information from a few general books or encyclopedias in your school library. 

In high school, your teachers might expect you to start using information from academic articles and more specific books. You might use encyclopedias and general works as a starting point, but you’ll be expected to go beyond them and do more work to synthesize information from different perspectives or different types of sources. You may also be expected to do “primary research,” where you study the source material yourself, instead of synthesizing what other people have written about the source material.

In college, you’ll be required to use academic journals and scholarly books, and your professors will now expect that you be more critical of these secondary sources, noticing the methodology and perspectives of whatever articles and books you’re using. 

In more advanced college courses, you’ll be expected to do more exhaustive surveys of the existing literature on a topic. You’ll need to conduct primary research that makes an original contribution to the field—the kind that could be published in a journal article itself.

For a walkthrough of the 12 essential steps to writing a good paper, check out our step-by-step guide .

Working on a research paper? Grab our free checklist to make sure your essay has everything it needs to earn an A grade.

Get the essential essay checklist

What makes a good research paper topic?

One of the most important features of a research paper topic is that it has a clear, narrow focus. 

For example, your teacher may assign you to write a research paper related to the US Revolutionary War. Does that mean that your topic should be “the US Revolutionary War”? 

Definitely not! There’s no way to craft a good paper with in-depth research with such a broad topic. (Unless you’re in elementary or middle school, in which case it’s okay to have a more general topic for your research paper.)

Instead, you need to find a more specific topic within this broader one. There are endless ways that you can make this narrower! Some ideas generated from this one broader topic might be:

• Causes of the US Revolutionary War
• Changes in military strategy during the Revolutionary War
• The experiences of Loyalists to England who remained in the American colonies during the Revolutionary War
• How the Revolutionary War was pivotal for the career of Alexander Hamilton
• The role of alliances with France during the US Revolutionary War
• The experiences of people of color during the Revolutionary War
• How George Washington’s previous military career paved the way for his leadership in the Revolutionary War
• The main types of weaponry during the Revolutionary War
• Changes in clothing and fashion over the courses of the Revolutionary War
• How Valley Forge was a key moment in the Revolutionary War
• How women contributed to the Revolutionary War
• What happened in Amherst, Massachusetts during the Revolutionary War
• Field medicine during the Revolutionary War
• How the Battle of Saratoga was a turning point in the Revolutionary War
• How different opinions about the Revolutionary War were reflected in poetry written during that time
• Debates over abolition during the Revolutionary War
• The importance of supply chains during the Revolutionary War
• Reactions to the US Revolutionary war in Europe
• How the US Revolutionary war impacted political theory in England and France
• Similarities and differences between the US Revolutionary War and the French Revolution
• Famous paintings inspired by the US Revolutionary War
• Different ways that the US Revolutionary War has been depicted in modern contemporary culture
• The appropriation of the “Boston Tea Party” by US politicians in the 2010s

This list could go on forever!

In fact, any of these topics could become even more specific. For example, check out the evolution of this topic:

• Economic causes of the Revolutionary war
• The way that tax policies helped lead to the Revolutionary War
• How tax laws enacted 1763–1775 helped lead to the Revolutionary War
• How the tax-free status of the British East India Company helped lead to the Revolutionary War
• How the 1773 tax-free status of the British East India Company helped lead to the Revolutionary War, as reflected in letters written 1767–1775
• How the 1773 tax-free status of the British East India Company helped lead to the Revolutionary War, as reflected in letters written by members of the Sons of Liberty 1767–1775

As you advance in your educational career, you’ll need to make your topic more and more specific. Steps 1–3 of this topic might be okay in high school, but for a college research paper steps 4–7 would be more appropriate!

As you craft your research paper topic, you should also keep in mind the availability of research materials on your subject. There are millions of topics that would make interesting research papers, but for which you yourself might not be able to investigate with the primary and secondary sources to which you have access.

Access to research materials might look like:

• To the best of our knowledge, the sources exist somewhere
• The source isn’t behind a paywall (or you or your school can pay for it)
• Your school or local library has a copy of the source
• Your school or local library can order a copy of the source for you
• The source is in a language that you speak
• The source has been published already (there’s tons of amazing research that hasn’t been published yet, a frustrating problem!)
• You can access the archive, museum, or database where the primary source is held—this might mean online access or travel! To access a source in an archive or museum you’ll often need permission, which often requires a letter of support from your school.

If you’re not sure about access to source materials, talk to a librarian! They’re professionals for this question.

Finally, pick a research topic that interests you! Given that there are unlimited research topics in the world and many ways to adapt a broad topic, there should absolutely be a way to modify a research topic to fit your interests.

Want help learning to write an amazing research paper? Work one-on-one with an experienced Ivy-League tutor to improve your writing skills or sign up for our bestselling academic writing workshop .

Insider tips to generate your own research paper topic

Use these formulas to generate your own research paper topics:

• How did X change over a period of time (year, decade, century)?
• What is the impact (or consequences) of X?
• What led to X?
• What is the role of X in Y?
• How did X influence Y?
• How did X become Y?
• How was X different from Y?
• How is X an example of Y?
• How did X affect Y?
• What were some reactions to X?
• What are the most effective policies to produce X result?
• What are some risks of X?
• How is our current understanding of X incorrect? (advanced)
• What happens if we look at X through the lens of Y theory or perspective? (advanced)

A good research paper topic often starts with the question words—why, how, what, who, and where. Remember to make it as specific as possible!

Good research paper topics

These research paper topics have been vetted by a Princeton grad and academic book editor!

• How did European rivalries (British vs French) impact North American history?
• What was the role of British and French alliances with indigneous tribes during the Seven Years’ War?
• Reactions to the 1754 Albany Congress among North American intellectual figures
• How the Albany Plan served as a model for future attempts at union among the North American colonies
• How did different religious identities (Calvinist, Catholic, etc.) play a role in the aftermath of the Seven Years’ War?
• What were the consequences of the 1763 Treaty of Paris?
• How did the Seven Years’ War impact British debt and colonial economics?
• What were some causes of the US Revolutionary War?
• How did military strategy change during the Revolutionary War?
• What were the experiences of Loyalists to England who remained in the American colonies during the Revolutionary War?
• How was the Revolutionary War pivotal for the career of Alexander Hamilton?
• What was the role of alliances with France during the US Revolutionary War?
• What were the experiences of people of color during the Revolutionary War?
• How did George Washington’s previous military career pave the way for his leadership in the Revolutionary War?
• What were the main types of weaponry during the Revolutionary War? How did that affect the options for military strategies?
• How did clothing and fashion change over the courses of the Revolutionary War?
• How was Valley Forge a key moment in the Revolutionary War?
• How did women contribute to the Revolutionary War?
• What happened in Amherst, Massachusetts (or any other specific location) during the Revolutionary War?
• What was field medicine like during the Revolutionary War? 
• How was the Battle of Saratoga a turning point in the Revolutionary War?
• How were different opinions about the Revolutionary War reflected in poetry written during that time?
• What were the debates over abolition during the Revolutionary War?
• What was the role of supply chains during the Revolutionary War?
• What were reactions to the US Revolutionary war like in Europe? What does that tell us about politics in England, France, the Netherlands, etc?
• How did the US Revolutionary war impact political theory in England and France?
• What are similarities and differences between the US Revolutionary War and the French Revolution?
• What are some famous paintings inspired by the US Revolutionary War? What do differences between these paintings tell us about how the artists who created them saw the war?
• What are some different ways that the US Revolutionary War has been depicted in modern contemporary culture? What does that tell us?
• How was the story of the “Boston Tea Party” appropriated by US politicians in the 2010s, and why?
• What was the difference between the Federalists and the Jeffersonians?
• How did the 1797 XYZ Affair lead to the Quasi-War with France?
• How were loans from European countries and companies (France, Spain, Dutch bankers) key to the early US?
• What were reactions to the Constitutional Convention of 1787?
• Why did the US remain neutral during the French Revolution?
• How did the Alien and Sedition acts contribute to the election of Thomas Jefferson as president?
• What was the US’s reaction to the Haitian revolution? Why did the US not recognize Haitian independence until 1862?
• What were the reactions to John Jay’s Treaty of 1794?
• How have the remarks made by George Washington in his Farewell Address inspired isolationist policies?
• How did interpretations of the Monroe Doctrine change over the decades since its creation? 
• How did the Roosevelt Corollary and Lodge Corollary change and expand the Monroe Doctrine?
• How did the presence of US companies like the United Fruit Company affect US military interventions in Latin America? 
• How was the Monroe Doctrine invoked in the Cuban Missile Crisis of 1962? 
• How was US culture shaped by the Cold War?
• How did ecology play a role in the rise of Ancient Egypt?
• How did water management technologies impact Ancient Egypt?
• How did bureaucracies function in Ancient Egypt?
• How did Egyptian art influence Ancient Greek art?
• Who could be a citizen in Athens in the 5th century BCE? What does this tell us about classical Athenian society?
• What was the impact of the Peloponnesian War?
• What was the impact of Alexander the Great’s attempt to create an empire?
• How does the way that Alexander the Great is represented in art demonstrate conceptions about the relationship between the human and the divine?
• Was there a conception of race in the ancient world? How were these ideas different from our own modern conceptions of race?
• What was the role of debt slavery in the Roman republic? How were these policies ended, and what is the significance of the end of debt slavery? What kinds of slavery remained?
• To what degree does the movie Gladiator accurately the Roman Empire in 176–192 CE?
• What was the role of slavery in managing the large latifundia ?
• How and why did the emperor Constantine I adopt Christianity?
• How did patterns of urbanism in the latter Roman empire change? What does this tell us about challenges being faced at that time?
• What do reactions to the Byzantine empress Theodora tell us about ideas of gender in 6th-century Byzantium?
• How did scientific advancements in Islamic Spain influence the rest of Europe?
• What was the relationship between Muslim, Christian, and Jewish populations in Islamic Spain? How does this compare to the experience of Muslim and Jewish populations in Christian Spain?
• How did medieval troubadour poetry represent a new idea of romantic relationships?
• What are similarities and differences between medieval troubadour poetry and lyric poetry in Ancient Greece? 
• What do letters between women and popes tell us about gender, power, and religion in medieval Europe?
• In what ways was Hildegard of Bingen groundbreaking for her time?
• Who produced beer in medieval England, and what does this tell us about society?
• How did the adoption of hops affect the production and distribution of beer?
• How did beer production allow some women a way to be financially independent?
• How was clothing used to mark religious and cultural identities in 15th- and 16th-century Spain?
• How did print culture change relationships and courting in Georgian England?
• How did churches function as social gathering spaces in Georgian England?
• To what degree is Netflix’s Bridgerton series historically accurate?
• How did ideas of love change in the 18th century? How did philosophy play a role in this?
• When were Valentine cards first commercially available? What does that show us about cultural ideas of love and courtship?
• What were the consequences of the desertification of the Sahara?
• How did trade links on the Red Sea influence Nubian culture?
• How did Carthage build power in Northern Africa around 600–500 BCE?
• What was the impact of the Mercenary War (241–238 BCE) in Carthage?
• How did the Roman province of Africa play a key role in financing the Roman Empire?
• What were the consequences of the Donatist division in the 300s in Northern Africa?
• What was the impact of the large-scale movement of Bedouins from the Arabian peninsula into the Maghreb?
• How was Mande society organized in the Mali Empire? 
• What was the role of the book trade in Timbuktu? What does this tell us about culture and learning in the Mali Empire?
• How did Aksum use trade to build wealth and power? 
• What do Nok terracotta sculptures tell us about Nok culture?
• How did the Luba Empire create a centralized political system? How did the idea of spiritual kins ( balopwe ) play a role in this system?
• How did tax collection work in the Lunda empire?
• What does it mean to say that the Ajuran Empire was a hydraulic empire? How did control over water resources allow the Ajuran Empire to build and consolidate power?
• What is the significance of diplomatic ties between the Somai Ajuran Empire and Ming dynasty China? 
• How did the tribute system in the Kingdom of Kongo help to stimulate interregional trade?
• What was the impact of the introduction of maize and cassava to the Kingdom of Kongo?
• How did women wield influence in the Kingdom of Benin?
• How did the Industrial Revolution in Europe help lead to the Scramble for Africa 1878–1898?
• What were the consequences of the Second Boer War?
• What happened in the Year of Africa (1960)?
• How did the Han dynasty consolidate power in frontier regions? 
• How and why did the Han dynasty nationalize the private salt and iron industries in 117 BCE?
• What are the earliest records of papermaking, and what is the significance of this invention?
• What was the role of Daoist religious societies in rebellions at the end of the Han dynasty (Yellow Turban Rebellion, Five Pecks of Rice Rebellion)?
• What do tomb paintings tell us about ancient Chinese society?
• What was the impact of the Sui dynasty’s standardization and re-unification of the coinage?
• What was the role of standardized testing in Sui dynasty and Tang dynasty China?
• Why is the Tang dynasty often regarded as a golden age of cosmopolitan culture in Chinese history?
• What was the role of slavery in imperial China? 
• How did the rise of jiedushi (regional military governments) undermine the civil-service system? What were the consequences of this?
• How did Tang dynasty China exert power over Japan and Korea?
• What was the Three Departments and Six Ministries system in imperial China and how did it work?
• What does the appearance of Inca, Maya, and Aztec goods in North America (Utah, Canada) and the appearance of goods from the Great Lakes region in Maya and Aztec ruins tell us about trade in the Pre-Columbian Americas?
• How did celebration of maize play a central role in Mesoamerican cultures?
• How did the Aztec empire use relationships with client city-states to establish power? How did the Aztec empire use taxation to exert power?
• How did the luxury good trade impact Aztec political power? 
• How did the building of roads play a key role in the Aztec empire?
• How and why has archaeology played a pivotal role in expanding our understanding of the pre-Columbian Americas?
• What are some common misconceptions about the Americas in the year 1491? Why do these misconceptions exist?

Latin American History (post-1492)

• How and why did the Spanish appropriate Aztec sites of significance (e.g. Mexico City at the site of Tenochtitlan)?
• What were reactions among Latin American intellectuals (e.g. Luis María Drago, Alejandro Álvarez and Baltasar Brum) to the Monroe Doctrine?
• How was the US’s involvement in the Venezuela Crisis of 1902–1903 a pivotal turning point in the relationship between the US and Latin American countries?
• What were the effects of the US’s involvement in the Cuban War for Independence?
• How did the Roosevelt Corollary of 1904 benefit the US?
• How did Simon Bolivar’s time in Europe affect his ideas about Latin American independence?
• How did 19th century academic societies play a role in the advancement of scientific discoveries? Who was excluded from these societies?
• How was music connected to the sciences in medieval thinking?
• When was the concept of zero first used, and how was it instrumental for advancements in math?
• What role did Islamic Spain play in the spread of scientific advancements in medieval Europe?
• What role has translation between languages played in the development of sciences?
• Why were Galileo’s ideas about astronomy controversial at the time?
• What was the connection between art and advancements in human anatomy?
• Why were Darwin’s ideas about natural selection controversial at the time?
• To what degree does the film Master and Commander accurately depict the voyages of Charles Darwin?
• How did the discovery of quinine and other medical innovations help to facilitate the European colonization of Africa?
• How and why was the internet invented?
• Does Virgil’s Aeneid celebrate the new Roman Empire or subvert it?
• Why was the poet Ovid exiled from Rome?
• What are the pagan influences in Beowulf ? What are the Christian elements in Beowulf ? What does that tell us about late Anglo-Saxon England?
• How does Chaucer’s Canterbury Tales reflect gender roles in late medieval England?
• How does Dante’s Inferno draw on book IV of Virgil’s Aeneid ? 
• How are gender roles presented and subverted in Shakespeare’s plays?
• To what degree did Henry David Thoreau live out the ideals he described in Walden in his own life?
• How did the serialized publication of novels affect the way that they were written?
• Does Dickens’ novel A Tale of Two Cities accurately portray the French Revolution?
• How did 18th-century novels propagate the idea of marrying for love?
• What did contemporary readers think about Jane Austen and her novels?
• To what degree do Jane Austen’s novels reflect economic realities for women in Regency England? What do they leave out?
• How did Lord Byron’s personal life affect his poetry?
• What do we know about the romantic life of Emily Dickinson?
• What were the religious movements that influenced the writer George Eliot, and how do those influences appear in her novels?
• In what ways were Walt Whitman’s writings new or different?
• How did British poets react to the horrors of Word War I?
• What do Tolkien’s letters reveal about the ways in which the two world wars influenced his writings?
• How did the friendship between CS Lewis and Tolkien affect their respective writings?
• What are the arguments for and against Catalonian independence from Spain?
• What are the arguments for and against Scottish independence from the United Kingdom?
• What are some risks of contact sports, especially for children?
• What are the most effective policies for combating childhood obesity?
• What are the most effective policies for reducing gun violence?
• Which countries have the longest life expectancy and why?
• What are some differences between the healthcare system in the US and in European countries? Which country has the most similar system to the US?
• What policies for parental leave exist in different countries? What are some effects of these policies?
• Has the drinking age in the US always been 21? What have been some different policies, and what were some consequences of them?
• What is the debate around museum artifacts like the Elgin Marbles in London or the Benin Bronzes in Berlin?
• How have politicians attempted to control population growth in different countries, either directly or indirectly? What have been some effects of these policies?
• Which countries have the most gender parity reflected in national governments? How have they accomplished this?
• How has public funding of K-12 education changed since the 1930s in the US? 
• How has public funding of higher education changed in the US?
• What is early childhood education like in different countries?
• What are some effects of free or reduced-cost meals in schools?
• How does access to menstrual products affect education outcomes for girls in different countries?
• What was the impact of Rousseau’s writings on education?
• How did Plato’s ideal forms of government reflect contemporary Athenian concerns about the unruly masses ( demos )?
• How did Aristotle justify slavery?
• How has wealth inequality increased in recent decades?
• How is inflation calculated, and what are the implications of this methodology?
• How have genetically-engineered crops changed the way that the planet feeds itself?
• How has animal testing changed since 2000?
• How is animal testing regulated differently in different countries?

Health Sciences and Psychology

• How do different societies reflect the natural circadian rhythms of the human body?
• How does secondhand smoke affect the human body?
• How does lack of sleep affect the body?
• How does stress affect the body?
• What are some ways to reduce stress?
• How have cancer treatments changed in the past 30 years?
• Why is it hard to find a “cure” for cancer?
• How has the Human Genome Project changed medical science?
• How were the Covid vaccines developed so quickly? What is the difference between the various Covid vaccines that have been developed?

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This paper is in the following e-collection/theme issue:

Published on 17.4.2024 in Vol 26 (2024)

This is a member publication of National University of Singapore

Comparing Open-Access Database and Traditional Intensive Care Studies Using Machine Learning: Bibliometric Analysis Study

Authors of this article:

Original Paper

• Yuhe Ke 1 * , MBBS   ; 
• Rui Yang 2 * , MSc   ; 
• Nan Liu 2 , PhD  

1 Division of Anesthesiology and Perioperative Medicine, Singapore General Hospital, Singapore, Singapore

2 Centre for Quantitative Medicine, Duke-NUS Medical School, National University of Singapore, Singapore, Singapore

*these authors contributed equally

Corresponding Author:

Nan Liu, PhD

Centre for Quantitative Medicine

Duke-NUS Medical School

National University of Singapore

8 College Road

Singapore, 169857

Phone: 65 66016503

Email: [email protected]

Background: Intensive care research has predominantly relied on conventional methods like randomized controlled trials. However, the increasing popularity of open-access, free databases in the past decade has opened new avenues for research, offering fresh insights. Leveraging machine learning (ML) techniques enables the analysis of trends in a vast number of studies.

Objective: This study aims to conduct a comprehensive bibliometric analysis using ML to compare trends and research topics in traditional intensive care unit (ICU) studies and those done with open-access databases (OADs).

Methods: We used ML for the analysis of publications in the Web of Science database in this study. Articles were categorized into “OAD” and “traditional intensive care” (TIC) studies. OAD studies were included in the Medical Information Mart for Intensive Care (MIMIC), eICU Collaborative Research Database (eICU-CRD), Amsterdam University Medical Centers Database (AmsterdamUMCdb), High Time Resolution ICU Dataset (HiRID), and Pediatric Intensive Care database. TIC studies included all other intensive care studies. Uniform manifold approximation and projection was used to visualize the corpus distribution. The BERTopic technique was used to generate 30 topic-unique identification numbers and to categorize topics into 22 topic families.

Results: A total of 227,893 records were extracted. After exclusions, 145,426 articles were identified as TIC and 1301 articles as OAD studies. TIC studies experienced exponential growth over the last 2 decades, culminating in a peak of 16,378 articles in 2021, while OAD studies demonstrated a consistent upsurge since 2018. Sepsis, ventilation-related research, and pediatric intensive care were the most frequently discussed topics. TIC studies exhibited broader coverage than OAD studies, suggesting a more extensive research scope.

Conclusions: This study analyzed ICU research, providing valuable insights from a large number of publications. OAD studies complement TIC studies, focusing on predictive modeling, while TIC studies capture essential qualitative information. Integrating both approaches in a complementary manner is the future direction for ICU research. Additionally, natural language processing techniques offer a transformative alternative for literature review and bibliometric analysis.

Introduction

The start of critical care as a medical subspecialty can be traced back to a polio epidemic during which a substantial number of patients needed prolonged mechanical ventilation [ 1 ]. Over time, the field of critical care has experienced significant growth and continual evolution. Research in this field has played a pivotal role in unraveling the complexities of numerous diseases and treatment modalities, driving substantial advancements in clinical practice over the past decades [ 2 ]. Groundbreaking studies have investigated critical areas such as sepsis, mechanical ventilation, acute lung and kidney injuries, intensive care unit (ICU) delirium, and sedation in critically ill patients [ 3 ].

These research studies have often been conducted in traditional ways such as prospective and randomized controlled trials [ 4 ], cohort and observational studies, clinical trials [ 5 ], and clinical and translational research [ 6 ]. These traditional methods have revolutionized patient care and improved outcomes significantly. For instance, the implementation of protocol-driven, goal-directed management of sepsis and appropriate fluid therapy has led to remarkable reductions in mortality rates [ 7 , 8 ], and these findings have been integral in developing evidence-based practice guidelines that are now the gold standard [ 9 , 10 ].

Despite their undeniable merits, traditional research methods in intensive care also come with several limitations [ 11 ]. Clinical trials are known for their high costs [ 12 ], stringent standardization requirements, and ethical oversight [ 13 ]. Data collection can be laborious, prone to human errors, and constrained in terms of quantity and granularity [ 14 ]. Moreover, obtaining patient consent for most randomized controlled trials in the ICU poses challenges [ 15 ], necessitating alternative consent models. These limitations have become increasingly apparent as medical complexity continues to grow exponentially [ 16 ].

The advent of electronic health records (EHRs) has heralded a new era in clinical research by facilitating the digitization of health care systems [ 17 ]. In this era of data science, a more integrated approach can be adopted, using machine learning (ML) algorithms to tackle the complexity of critical illness [ 18 ]. Open-access databases (OADs), such as the Medical Information Mart for Intensive Care (MIMIC) database [ 19 ] and the Philips eICU Collaborative Research Database (eICU-CRD) [ 20 ], have played a transformative role by enabling free data sharing.

The concept of free and open databases plays a pivotal role in promoting data sharing and advancing medical knowledge in accordance with the findable, accessible, interoperable, and reusable (FAIR) guiding principle. The FAIR principles, which emphasize that data should be findable, accessible, interoperable, and reusable, are essential for fostering a collaborative and transparent scientific research environment [ 21 , 22 ]. By removing barriers to access, free, and open databases allow researchers, regardless of their affiliations or resources, to contribute to and benefit from the collective pool of information. Accessibility fosters inclusivity and diversity in research, promoting a broader range of perspectives and approaches to medical challenges. This democratization of knowledge leads to a more equitable distribution of information. Researchers can now leverage these vast repositories of information for ML and artificial intelligence studies, marking a departure from traditional intensive care (TIC) research approaches.

Conducting a literature review [ 23 ] to investigate the disparities between traditional ICU research and studies based on open-access data sets holds significant importance as it provides a comprehensive understanding of the strengths and limitations of the latter. However, conventional methods of literature reviews and bibliometric analysis have their limitations, especially when dealing with large-scale literature due to computational complexity and the labor-intensive nature of manual interpretations [ 24 - 26 ]. To address these challenges, natural language processing (NLP) offers a promising avenue, while topic modeling techniques can be used to extract various topic themes from extensive data sets [ 27 , 28 ].

Built on the foundations of bidirectional encoder representations from transformers (BERT), BERTopic introduces a novel approach to topic modeling [ 29 , 30 ]. Unlike traditional unsupervised models like latent Dirichlet allocation, which rely on “bag-of-words” model [ 31 ], BERTopic overcomes the problem of semantic information loss, significantly enhancing the accuracy of generated topics, and providing more interpretable compositions for each topic, which greatly facilitates the classification of topics.

With the aid of BERTopic, this study aims to shed light on the disparities and commonalities between studies conducted through OADs and TIC research. By analyzing the overall trends and patterns in these 2 groups, we seek to identify knowledge gaps and explore avenues for complementary contributions between these research approaches.

Data Filtering

We performed an ML-based analysis of research abstracts in the Web of Science (WoS) database to automatically categorize the research papers to conduct this literature mapping analysis. There was no limit to the year of publication of the articles. The search query consisted of the following keyword to identify all the studies that were published under the umbrella of intensive care: (“ICU” OR “intensive care”). The search terms were deliberately left to be broad to cover broad spectrums of journals in the field.

The inclusion criteria were as follows: (1) written in English, (2) articles that had keywords related to intensive care, (3) articles that had the article type of “article” or “review.” We excluded articles with incomplete data fields (eg, title, abstract, publication year, and paper citation). The articles included were then further processed to identify if they were studies using OADs. These articles were labeled as “open-access database,” while the rest of the articles extracted were labeled as “traditional intensive care.”

The search used for this study was performed on January 18, 2023, from WoS. This generated 227,893 search results, which were subsequently reselected using Python. An advanced search from PubMed was done based on the broad search terms of ICU studies used from previous Cochrane ICU literature review [ 32 ] to ensure the accuracy of the results. The numbers corroborated with a discrepancy of 4.9% (227,893 WoS keyword search vs 239,748 PubMed ICU keyword search).

Selection Criteria for OADs

A title search using keywords from all currently existing OADs was conducted to identify OAD studies. These include (1) MIMIC [ 19 ], (2) eICU-CRD [ 20 ], (3) Amsterdam University Medical Centers Database (AmsterdamUMCdb) [ 33 ], (4) High Time Resolution ICU Dataset (HiRID) [ 34 ], and (5) Pediatric Intensive Care database [ 35 ]. We avoided including only keywords in the search and restricted the search years by the year that the OAD was made publicly available to reduce the inadvertent inclusion of incorrect articles due to keywords. For instance, the search term for OADs published with the MIMIC database included title keyword search with the terms (“MIMIC-IV” OR “MIMIC-III” OR “MIMIC-II” OR “MIMIC Dataset” OR “medical information mart for intensive care” OR “MIMIC IV” OR “MIMIC III” OR “MIMIC II”) in studies that were published after 2003. The title keyword search for the searches and the year of cutoff for each OAD are presented in Multimedia Appendix 1 .

Furthermore, to ensure the accuracy of the supervised keyword classification, a manual review of the classification by 2 critical care physicians was done for 100 articles from each category that were randomly selected. The review was done independently with the physicians labeling the extract publications into OAD and TICs. An accuracy of 99% was achieved on independent reviews, and full agreement was achieved after discussion on the discrepancy. The final results were matched with the supervised keyword classification.

We performed a bibliometric analysis by directly extracting publication details from the WoS database using Python (Python Software Foundation). The analysis involved assessing the number of articles published per year, calculating total citation counts, and identifying the top journals that published intensive care-related articles. Comprehensive results are presented in Multimedia Appendix 2 .

Data Analysis

Uniform manifold approximation and projection.

Uniform manifold approximation and projection (UMAP) is a manifold learning technique for dimension reduction, which can identify key structures in high-dimensional data space and map them to low-dimensional space to accomplish dimensionality reduction. Compared to other dimensionality reduction algorithms, such as principal component analysis [ 36 ], UMAP can retain more global features [ 37 ]. In this paper, we constructed a corpus consisting of abstract words from all studies. However, due to the massive size of the corpus, visualizing and analyzing the high-dimensional data to explore the differences in the vocabulary patterns between the OAD and TIC studies is a challenge. The UMAP package in Python, which implements the UMAP algorithm, was used to project the high-dimensional corpus to 4 dimensions. By cross plotting each dimension, we were able to investigate underlying differences in corpus distribution between OAD and TIC studies.

Topic modeling can help us explore the similarities and differences between research topics in OAD and TIC studies. Unlike conventional topic modeling models, BERTopic uses the BERT framework for embeddings, enabling a deeper understanding of semantic relationships [ 30 ]. The BERTopic model was implemented by the BERTopic package in Python and divided 146,727 studies into 30 topic IDs. We also performed latent Dirichlet allocation topic modeling through Python’s LdaModel package for comparison. Through the review of topic keywords by 2 critical care physicians, BERTopic exhibited superior accuracy and sophistication in topic identification, with enhanced interpretability and scientific rigor.

Consequently, the BERTopic model was used for the final analysis. Each of these topics was given a corresponding clinical research category. The overlapping categories were merged into topic families for easier comparisons. By using these advanced techniques, we were able to uncover hidden patterns and relationships within the literature and provide insights into the current state of intensive care research.

A total of 227,893 records were identified from the WoS database on January 18, 2023, of which 195,463 full records were subsequently processed. Records were excluded if they are not “article” or “review” or if they do not contain keywords related to intensive care. After exclusions, 145,426 articles were identified as TIC studies and 1301 articles were categorized as OAD ( Figure 1 ).

We examined the number of articles published per year to analyze the trends in TIC and OAD studies ( Figure 2 ). Over the past 2 decades, TIC studies have experienced exponential growth, culminating in a peak of 16,378 articles in 2021. A subsequent decline in the number of publications occurred in 2022, likely attributable to delayed indexing within the WoS database and a reduction in COVID-19–related studies as the pandemic stabilized [ 38 ]. In contrast, the first OAD study emerged in 2003, with its popularity experiencing a consistent upsurge since 2018. Nonetheless, the number of OAD publications remains markedly lower in comparison to TIC publications.

The OAD studies were published most frequently in new open-access journals such as Frontiers in Medicine , Frontiers in Cardiovascular Medicine , and Scientific Reports while the TIC studies were published most frequently in established journals like Critical Care Medicine , Intensive Care Medicine , and Critical Care ( Multimedia Appendix 2 ). Further analysis of keywords from the abstracts showed 2.4% (3492/145,426) TIC studies were meta-analyses or systematic reviews, while only 0.08% (1/1301) OAD study was in this category. There were 5.61% (73/1301) OAD studies, and 7.43% (10,799/145,426) TIC studies that had the keyword of “cost.” Examples of the data fields that are available within OADs such as MIMIC and eICU-CRD are listed in Textbox 1 . Some information fields such as end-of-life goals and values and health care provider psychology are not available within the current EHRs extracted for OADs.

Examples of information that is available in current OADs

• Patient information: demographics and social set-up
• Hospital context: admission time and discharge time, intensive care unit (ICU) and hospital admissions, and pre-ICU admission
• Diagnosis: physician-curated ICU diagnosis and data-driven phenotypes
• Intervention: medications, procedures, and organ support
• Diagnostics: blood test, microbiology, and scans
• Clinical texts: clinical notes and diagnostic reports
• Physiological monitoring: basic monitoring and waveforms

Examples of information that is not readily available in current OADs

• Patient information: family set up and visiting, financial information, and special populations
• Hospital context: post-ICU discharge details, delayed admission or discharge, and health personnel psychology
• Diagnosis: pre-ICU history and diagnosis requiring clinical symptoms
• Intervention: indications for interventions, complications, and intraoperative and postoperative
• Diagnostics: pathology photographs, imaging, and molecular or genetic studies
• Clinical texts: patient narratives, end-of-life goals and patient value, and health personnel behavior
• Physiological monitoring: advanced monitoring

The UMAP algorithm was used to project the high-dimension corpus to 4 dimensions and allowed exploration of the vocabulary patterns between the OAD and TIC studies ( Figure 3 ). The projection values are represented by the x-axis, while the densities are represented by the y-axis. The presence of considerable overlap between TIC studies and OAD studies suggests that they share a substantial number of common terminologies, which may correspond to similar research topics. Nonetheless, TIC studies exhibit a more extensive coverage than OAD studies, which may stem from broader research scope and extended research duration.

Subsequently, the BERTopic model was then used to generate 30 topic IDs ( Figure 4 ). The internal commonalities of each topic ID were reviewed by critical care physicians and assigned a specific subtopic in intensive care research. The model was able to automatically classify the topics with high interpretability and the topic components were interpreted with ease. For instance, components in topic ID 5 consist of, in decreasing order of weightage: “learning,” “model,” “machine,” “machine learning,” “models,” “data,” “prediction,” and “performance.” This topic was consequently labeled “predictive model” (topic ID 5 in Multimedia Appendix 3 ).

The overall topic distribution in TIC studies was more uniform, while the OAD studies tended to be concentrated on several topics including topic ID 2 (kidney injury), 5 (predictive model), and 13 (sepsis). Some topics that were missing in OAD studies included 6 (pediatrics care), 21 (viral infections), 23 (health personnel and psychology), and 28 (nutrition and rehabilitation).

The similarity matrix shows that there was little overlap between the topics ( Multimedia Appendix 4 ). To facilitate the interpretability of the categories, the overlapping topic IDs were merged to form the final 22 topic families ( Multimedia Appendix 3 ).

Topics such as “healthcare associated infection,” “thoracic surgeries,” and “pregnancy related” research were among the more frequently discussed 15 topics in TIC studies but have limited publications in OAD studies. The topics of “predictive model,” “obesity,” and “fungal infections” were popular in OAD studies but not the TIC studies. Overall, the topic distributions of the TIC studies were distributed more evenly with the topic family of sepsis accounting for a quarter of the studies, while publications in the OAD studies were heavily skewed toward the predictive model (>40%) and sepsis (>30%; Figure 5 ).

Principal Results

This study conducted a comprehensive review and bibliometric analysis of OAD and TIC studies. NLP was used to facilitate this large-scale literature review. Studies using OADs mainly concentrated on a few topics, such as predictive modeling, while TIC studies covered a wider range of topics with a more balanced distribution.

Advantages of OAD Studies

OAD studies offer several advantages that have contributed to their increasing popularity in intensive care research. The granularity of data and easy access to large-cohort databases, such as MIMIC [ 39 ], has enabled researchers to perform predictive modeling and conduct various secondary analyses efficiently [ 40 , 41 ]. This accessibility has provided valuable opportunities for exploring specific aspects of patient care, evident in studies investigating phenomena like “weekend effects” and circadian rhythms in ICU patients before discharge [ 42 - 46 ]. The vast amount of longitudinal and time series data available in OADs has also facilitated the implementation of complex ML and deep learning methods [ 47 ].

Limitations of OAD Studies

However, it is crucial to acknowledge the retrospective nature of OAD data, which inherently limits the assessment of confounding factors and the ability to draw strong causal conclusions. The observational design of OAD studies may result in lower-quality evidence according to the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework [ 48 , 49 ], and thus, the research from OAD studies has yet to be fully integrated into existing evidence-based guidelines, as exemplified by the omission of OAD studies in the 2021 sepsis guidelines [ 50 ]. Nevertheless, OADs remain a valuable resource for supplementing and complementing TIC studies, providing unique insights and enhanced predictive scores for intensive care settings.

Furthermore, approximately 50% of the studies using OADs published focused on predictive modeling. The increased usage of ML methods in predictive modeling has not been without critique. Some medical prediction problems inherently possess linear characteristics, and the selection of features may predominantly focus on already known strong predictors, leading to limited improvements in prediction accuracy with ML [ 51 ]. Additionally, interstudy heterogeneity poses a challenge in comparing results obtained from different ML models applied to the same data sets [ 52 ]. The ethical implications of relying solely on ML models to make high-risk health care decisions instead of involving clinical expertise are also relevant considerations [ 51 , 53 ].

While OADs provide comprehensive patient data, there are certain limitations in their ability to capture specific information essential for certain critical care research areas. Notably, data fields related to qualitative aspects such as ethics and end-of-life care [ 54 , 55 ], and health care personnel psychology [ 56 ] may be challenging, if not impossible, to obtain through OADs generated from EHRs. Consequently, TIC studies have played a pivotal role in addressing these limitations by capturing critical information that is integral to understanding ethical considerations, patient experiences, and health care provider psychology in intensive care [ 57 , 58 ].

Synergy Between OAD and TIC Studies

The synergy between OAD and TIC studies is a promising approach to enhance the comprehensiveness and robustness of intensive care research. OADs, with their large cohort sizes, can serve as external validation cohorts for ML models developed from TIC studies, potentially reducing the sample sizes required for prospective research. Furthermore, OAD studies can corroborate the results of TIC studies, benefiting from larger sample sizes and real-world data, thus providing more practical insights for implementation in intensive care settings [ 43 ]. The integration of OAD and TIC studies presents an opportunity to bridge the gaps in data availability and research methodologies, ultimately enriching the understanding and practice of critical care medicine.

Potential Impact of NLP

The usage of large language models such as BERTopic has proven to be a valuable tool for large-scale literature review and topic extraction [ 58 ]. This approach has enabled accurate, reliable, and granular topic generation, offering clinicians a more effective means of interpreting data compared to traditional bag-of-words models [ 59 ]. The potential of NLP to analyze scientific articles and identify trends and knowledge gaps holds promise for shaping the future of research in critical care medicine. As the volume of publications in critical care continues to grow and large language modeling continues to advance in health care [ 60 ], AI technology will be crucial in efficiently identifying and predicting emerging trends.

Future Directions

Future research in the field of critical care can explore novel applications of ML beyond predictive modeling. For instance, using ML to study patterns in how papers are cited, shared, and discussed on the web could help predict their potential impact on the scientific community. This analysis can aid in identifying highly influential papers and understanding the factors that contribute to their recognition. Additionally, investigations into methods for enhancing the interpretability and transparency of ML algorithms in critical care research would further facilitate the ethical and responsible use of AI technologies.

Strengths and Limitations

The study’s application of NLP-driven in analyzing scientific articles and identifying trends highlights the potential impact of AI technologies in streamlining literature reviews and identifying emerging trends more efficiently.

Another notable strength of this study is the usage of the WoS database, the world’s oldest and most extensively used repository of research publications and citations, encompassing approximately 34,000 journals [ 61 ]. The comprehensiveness of this database provides a robust representation of the literature in the field of intensive care research. Nevertheless, it is essential to acknowledge that some articles published in nonindexed journals might not have been captured, and future studies could benefit from considering additional databases to supplement our findings.

One other limitation lies in the classification of OAD and TIC studies, which may be subject to variations in the interpretation of keywords. However, we optimized the keyword combinations during the search process in the WoS database and implemented Python filtering techniques, resulting in a relatively high level of accuracy in our classifications. The number of studies was further corroborated with a manual search on PubMed and a review of the classifications of the studies was done by critical care physicians.

Although there were no specific language restrictions, the nature of the search term being in English inadvertently excluded valuable contributions from non-English research. This may potentially limit the generalizability of our findings to a broader international audience. In future investigations, the inclusion of articles from various languages could offer a more comprehensive and diverse perspective on intensive care research.

Conclusions

This study has provided valuable insights into the expanding landscape of intensive care research through a comprehensive bibliometric analysis of a large number of publications by leveraging NLP technologies. While OAD studies have demonstrated significant promise, it is essential to view them as a complementary approach rather than a replacement for TIC studies. The unique strength of TIC studies lies in their ability to capture crucial qualitative information, which is essential for comprehensive and ethical decision-making. The integration of both OAD and TIC studies offers a synergistic approach to enriching our understanding of critical care medicine and advancing patient care outcomes. As NLP technology continues to advance, it holds the potential to offer a feasible and transformative alternative for literature review and bibliometric analysis.

Acknowledgments

We thank Dr Nicholas Brian Shannon for assistance with the manual review of the supervised keyword classification. This work was supported by the Duke-NUS Signature Research Programme, funded by the Ministry of Health, Singapore.

Data Availability

The data sets generated during and/or analyzed during this study are available from the corresponding author on reasonable request. The complete set of code used in this study is readily available for download on GitHub [ 62 ].

Authors' Contributions

YK and NL played key roles in the conceptualization of the project. RY was responsible for formalizing the methodology and conducting data curation with the advisory of YK. YK contributed to the validation of the data, ensuring its relevance to the research objectives. RY took the lead in visualizing the data. Both YK and RY drafted the original manuscript. NL served as the project supervisor, overseeing the implementation, and providing valuable input in the writing, review, and editing phases.

Conflicts of Interest

None declared.

Search terms for open-access database (OAD) studies with the cutoff by the years of publications.

Top 20 journals ranked by total citation in which the open-access database and traditional intensive care studies were published. The average citation per article was obtained with the total citation/total number of articles. The citation counts were obtained from Web of Science.

Topic ID and topic family and the components and weightage in each of the categories.

Similarity matrix of 30 topics.

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Abbreviations

Edited by A Mavragani; submitted 19.04.23; peer-reviewed by D Chrimes, S Pesälä; comments to author 14.07.23; revised version received 01.08.23; accepted 14.01.24; published 17.04.24.

©Yuhe Ke, Rui Yang, Nan Liu. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 17.04.2024.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in the Journal of Medical Internet Research, is properly cited. The complete bibliographic information, a link to the original publication on https://www.jmir.org/, as well as this copyright and license information must be included.

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April 16, 2024

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New study sheds light on the structure and evolution of an enzyme in psychoactive fungi

by Friederike Gawlik, Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie - Hans-Knöll-Institut (Leibniz-HKI)

An international research team has investigated the biosynthesis of psilocybin, the main ingredient of hallucinogenic mushrooms. They gained new insights into the structure and reaction mechanism of the enzyme PsiM. It plays a key role in the production of psilocybin. The results of the study were published in the journal Nature Communications .

The psychoactive substance psilocybin is the most important natural product of so-called "magic mushrooms" of the genus Psilocybe, which makes these mushrooms a popular drug. However, psilocybin has also become increasingly interesting in medicine in recent years for a number of mental illnesses. It has shown promising results in the treatment of depression, addiction and anxiety. Psilocybin is therefore already at an advanced stage of clinical testing as an active pharmaceutical ingredient .

Psilocybin is formed by fungi in complex biochemical processes from the amino acid L-tryptophan. The enzyme PsiM, a methyltransferase, plays an important role in this process. It catalyzes two methylation reactions in succession, the last two steps in the production of psilocybin.

"There are many methyl transfer reactions in nature," says Dirk Hoffmeister. He is Professor of Pharmaceutical Microbiology at Friedrich Schiller University Jena and heads an associated research group at the Leibniz Institute for Natural Product Research and Infection Biology—Hans Knöll Institute (Leibniz-HKI). "Here, we asked ourselves how exactly psilocybin production is accomplished."

Two enzymes, one origin

To this end, a team from the Medical University of Innsbruck led by crystallographer Bernhard Rupp and the Jena researchers investigated the enzyme PsiM both biochemically and using X-ray crystal structure analysis. This method allows proteins to be visualized down to the atomic level , whereby several stages of the reaction could be depicted in ultra-high resolution.

Examination of the protein structure revealed astonishing similarities in structure between the fungal enzyme PsiM and enzymes that are normally responsible for the modification of RNA. Although there are also differences, the great structural similarity indicates that the fungal enzyme has evolved from a single methylating RNA methyltransferase.

Accordingly, it previously only had the ability to attach a single methyl group to the target molecule. "The psilocybin precursor norbaeocystin, which is converted by PsiM, structurally imitates part of the RNA, but is methylated twice," says Hoffmeister.

In further investigations, the researchers were also able to identify a crucial amino acid exchange that gave PsiM the ability to carry out double methylation during evolution. This process involves the final step in the entire reaction chain for potential biotechnological production of the active ingredient: the conversion of the single-methylated intermediate baeocystin to the double-methylated psilocybin.

A clear end

The researchers then wondered whether PsiM could also convert psilocybin to aeruginascin by attaching a third methyl group. Aeruginascin is an analog of psilocybin, which occurs naturally in some types of fungi.

"The only question is, where does it come from?" asks Hoffmeister. Until now, there has been disagreement in the scientific community as to whether the compound is a metabolic product of the psilocybin biosynthesis pathway and could arise from psilocybin through PsiM.

The study now provides a clear result: "This is clearly not the case," says Hoffmeister. "PsiM is not able to convert psilocybin to aeruginascin." PsiM can therefore be ruled out for the biosynthetic production of this analog. However, the enzyme could be relevant for the production of psilocybin in microorganisms in the future.

"Overall, our results can help to develop new variants of psilocybin with improved therapeutic properties and to produce them biotechnologically," says Hoffmeister.

Journal information: Nature Communications

Provided by Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie - Hans-Knöll-Institut (Leibniz-HKI)

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Microbiology articles from across Nature Portfolio

Microbiology is the study of microscopic organisms, such as bacteria, viruses, archaea, fungi and protozoa. This discipline includes fundamental research on the biochemistry, physiology, cell biology, ecology, evolution and clinical aspects of microorganisms, including the host response to these agents.

Video game unleashes millions of citizen scientists on microbiome research

Borderlands Science is a casual mini-game released within a mass-market video game that crowdsources the alignment of one million RNA sequences from the human microbiome. In 3 years, 4 million participants generated over 135 million puzzle solutions that were used to build a reference alignment and improve microbial phylogeny.

Nanoparticles subdue antibiotic-resistant bacteria’s defences while enhancing innate immunity

A method for overcoming antibiotic resistance uses multimodal nanoparticles that target bacterial defence mechanisms while enhancing the innate immune response.

• Julia C. Lang
• Keira Melican

Bacteria deploy umbrella toxins against their competitors

Bacteria make protein toxins to compete with other bacteria in microbial communities. A study of a common soil bacterium has revealed a previously unknown type of antibacterial toxin that forms a striking umbrella-like structure.

• Sarah J. Coulthurst

Related Subjects

• Antimicrobials
• Applied microbiology
• Bacteriology
• Bacteriophages
• Biogeochemistry
• Cellular microbiology
• Clinical microbiology
• Microbial communities
• CRISPR-Cas systems
• Environmental microbiology
• Industrial microbiology
• Infectious-disease diagnostics
• Microbial genetics
• Parasitology
• Phage biology
• Policy and public health in microbiology

Latest Research and Reviews

DNA glycosylases provide antiviral defence in prokaryotes

A screen utilizing an environmental DNA library in Escherichia coli is used to identify Brig1, a previously unknown anti-phage defence system with homologues across distinct clades of bacteria.

• Amer A. Hossain
• Ying Z. Pigli
• Luciano A. Marraffini

MmcA is an electron conduit that facilitates both intracellular and extracellular electron transport in Methanosarcina acetivorans

Methanogens conserve energy through methane generation, however the biochemical details of anaerobic respiration in methanogens remain unclear. Here, authors show a multiheme c -type cytochrome, MmcA, plays a critical role in methanogenesis and anaerobic respiration.

• Dinesh Gupta
• Keying Chen
• Dipti D. Nayak

Survival and rapid resuscitation permit limited productivity in desert microbial communities

Prompt physiological reactivation after rainfall pulses may be key for microbial survival in arid ecosystems. Here, the authors use stable isotope tracers, single-cell NanoSIMS and metatranscriptomics to shed light on how desert biocrust microbial communities respond to rewetting.

• Stefanie Imminger
• Dimitri V. Meier
• Dagmar Woebken

tRNA modification reprogramming contributes to artemisinin resistance in Plasmodium falciparum

Artemisinin-resistant Plasmodium falciparum can use tRNA modification reprogramming and codon bias translation as an epitranscriptomic response to survive artemisinin-induced stress.

• Jennifer L. Small-Saunders
• Ameya Sinha
• David A. Fidock

Streptomyces umbrella toxin particles block hyphal growth of competing species

Streptomyces are discovered to produce antibacterial protein complexes that selectively inhibit the hyphal growth of related species, a function distinct from that of the small-molecule antibiotics they are known for.

• Qinqin Zhao
• Savannah Bertolli
• Joseph D. Mougous

The buzz about honey-based biosurveys

• Paton Vuong
• Anna Poppy Griffiths
• Parwinder Kaur

News and Comment

Exploring the lung microbiome’s role in disease

Unusual microbial communities in a person’s lower airways could influence the onset and progression of lung cancer and other conditions, and might point the way to therapies.

• Anthony King

Deadly diseases and inflatable suits: how I found my niche in virology research

Virologist Hulda Jónsdóttir studies some of the world’s most pathogenic viruses at the Spiez Laboratory in Switzerland.

• Nikki Forrester

Reconciling trade-offs in pig farming requires a change in mitigation approach

We found trade-offs among the environmental and animal welfare impacts of pig farms — those that had low greenhouse gas emissions typically had low land use but poor animal welfare and high antimicrobial use. Some farms performed well in all four impacts, but these farms were not consistently associated with any particular farm or label type.

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