How to Write a Review Article

  • Types of Review Articles
  • Before Writing a Review Article
  • Determining Where to Publish
  • Searching the Literature
  • Citation Management
  • Reading a Review Article

Descriptions of Types of Reviews

Reproduced from: Grant MJ, Booth A. A typology of reviews: an analysis of 14 review types and associated methodologies .  Health Info Libr J . 2009 Jun;26(2):91-108. doi: 10.1111/j.1471-1842.2009.00848.x. Review. PubMed PMID: 19490148.

Further Reading

Sutton A, Clowes M, Preston L, Booth A. Meeting the review family: exploring review types and associated information retrieval requirements . Health Info Libr J. 2019;36(3):202-222. doi: 10.1111/hir.12276.

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Feature papers represent the most advanced research with significant potential for high impact in the field. A Feature Paper should be a substantial original Article that involves several techniques or approaches, provides an outlook for future research directions and describes possible research applications.

Feature papers are submitted upon individual invitation or recommendation by the scientific editors and must receive positive feedback from the reviewers.

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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Article Types

All articles are assigned a type, depending on the content of the article. This is useful to readers, informing them of the style of content to expect (original research, review, communication, etc.) and for indexing services when applying filters to search results. This section details the most common article types, although is not exhaustive. Editors have the final say on which type should be assigned to a published article.

These are original research manuscripts. The work should report scientifically sound experiments and provide a substantial amount of new information. The article should include the most recent and relevant references in the field. The structure should include an Abstract, Keywords, Introduction, Materials and Methods, Results, Discussion, and Conclusions (optional) sections, with a suggested minimum word count of 4000 words. Please refer to the journal webpages for specific instructions and templates.

Brief Report

Brief reports are short, observational studies that report preliminary results or a short complete study or protocol. Brief reports usually contain two figures and/or a table; however, the Materials and Methods sections should be detailed to ensure reproducibility of the presented work. The structure is similar to that of an article, and there is a suggested minimum word count of 2500 words.

Case Report

Common in medical journals, case reports present detailed information on the symptoms, signs, diagnosis, treatment (including all types of interventions), and outcomes of an individual patient. They usually describe new or uncommon conditions that serve to enhance medical care or highlight diagnostic approaches. The structure of case reports differs from articles and includes an Abstract, Keywords, Introduction, Detailed Case Description, Discussion, and Conclusions, with a suggested minimum word count of 2500 words. Special care should be taken when submitting case reports to ensure that appropriate permission for publication has been obtained from patients featuring in the paper. A sample blank consent form can be found on the ‘Instructions for Authors’ pages of the relevant journals. Please refer to the journal websites for more information, because not all MDPI journals publish case reports.

Communication

Communications are short articles that present groundbreaking preliminary results or significant findings that are part of a larger study over multiple years. They can also include cutting-edge methods or experiments, and the development of new technology or materials. The structure is similar to an article and there is a suggested minimum word count of 2000 words.

Conference Report

Conference reports are records of the events of a conference, seminar, or meeting. They should provide a comprehensive overview of a meeting or session, along with relevant background information for the reader. The structure should contain Abstract, Keywords, Introduction, Conference Sections, and Concluding Remarks, with a suggested minimum word count of 2500 words. They can also include all accepted meeting abstracts.

These are non-peer-reviewed texts used to announce the launch of a new journal, a new section, a new Editor-in-Chief, a Special Issue, or an invited editorial. The main text should provide a brief introduction of the purpose and aim of the Editorial—to present the new journal, close the Special Issue, report on a pressing topic, etc. Editorials should not include unpublished or original data, although must provide a Conflict of Interest statement. Editorials prepared for the launch of new journals may also include a short biography of the Editor-in-Chief.

Essays are an article type commonly used in humanities and social sciences to present provocative arguments aimed to stimulate the readers’ re-thinking of certain issues. The structure is similar to that of a review, with a suggested minimum word count of 4000 words. Arguments should be supported by relevant references.

Hypothesis articles introduce a new hypothesis or theory, or a novel interpretation of that theory. They should provide: (1) a novel interpretation of recent data or findings in a specific area of investigation; (2) an accurate presentation of previously posed hypotheses or theories; (3) the hypothesis presented which should be testable in the framework of current knowledge; and (4) the possible inclusion of original data as well as personal insights and opinions. If new data are presented, the structure should follow that of an article. If no new data are included, the structure can be more flexible, but should still include an Abstract, Keywords, Introduction, Relevant sections, and Concluding Remarks, with a suggested minimum word count of 4000 words.

Opinions are short articles that reflect the author’s viewpoints on a particular subject, technique, or recent findings. They should highlight the strengths and weaknesses of the topic presented in the opinion. The structure is similar to a review; however, they are significantly shorter and focused on the author’s view rather than a comprehensive, critical review. The suggested minimum word count is 2000 words.

Perspective

Perspectives are usually an invited type of article that showcase current developments in a specific field. Emphasis is placed on future directions of the field and on the personal assessment of the author. Comments should be situated in the context of existing literature from the previous 3 years. The structure is similar to a review, with a suggested minimum word count of 3500 words.

Project Report

Project reports are short and/or rapid announcements of project results and implications. They should include a research strategy or approach, the activities, technologies, and details of the project undertaken, conclusions, and recommendations for the future direction of work in the field. The structure is similar to an article, but permits a higher degree of flexibility. The suggested minimum word count is 3500 words.

Protocols provide a detailed step-by-step description of a method. They should be proven to be robust and reproducible and should accompany a previously published article that uses this method. Any materials and equipment used should be explicitly listed. Conditions, quantities, concentrations, etc., should be given. Critical timepoints and steps, as well as warnings, should be emphasized in the text. The structure should include an Abstract, Keywords, Introduction, Experimental Design, Materials and Equipment, Detailed Procedure, and Expected Results, with a suggested minimum word count of 4000 words.

Registered Report

Registered reports are scientific articles which are peer reviewed before the research is performed and the data are collected. The ideas that meet high scientific standards, such as rigor, soundness, significant importance, and implications for the scientific community are then provisionally accepted for publication before data collection starts. Detailed guidelines for registered reports can be accessed here: https://www.mdpi.com/about/article_types/registered_reports .

Technical Note

Technical notes are brief articles focused on a new technique, method, or procedure. These should describe important modifications or unique applications for the described method. Technical notes can also be used for describing a new software tool or computational method. The structure should include an Abstract, Keywords, Introduction, Materials and Methods, Results, Discussion, and Conclusions, with a suggested minimum word count of 3500 words.

Reviews offer a comprehensive analysis of the existing literature within a field of study, identifying current gaps or problems. They should be critical and constructive and provide recommendations for future research. No new, unpublished data should be presented. The structure can include an Abstract, Keywords, Introduction, Relevant Sections, Discussion, Conclusions, and Future Directions, with a suggested minimum word count of 4000 words.

Book Review

Book reviews are short literary criticisms analyzing the content, style, and merit of a recently published book. Full book details should be provided at the beginning of the article. The structure should only include an Introduction and be a discussion of critical points with no sections or conclusions, with a suggested minimum word count of 500 words.

Systematic Review

Systematic review articles present a detailed investigation of previous research on a given topic that use clearly defined search parameters and methods to identify, categorize, analyze, and report aggregated evidence on a specific topic. The structure is similar to a review, with a suggested minimum word count of 4000 words; however, they should include a Methods section. Systematic reviews should strictly follow the PRISMA checklist ( http://prisma-statement.org/PRISMAStatement/Checklist ) and include a completed PRISMA flow diagram as part of the main text or Supplementary Materials. Templates for the flow diagram can be downloaded from the PRISMA website. We strongly encourage authors to register their detailed protocols before data extraction commences, in a public registry such as PROSPERO ( https://www.crd.york.ac.uk/prospero/ ). Authors must include a statement about following the PRISMA guidelines and registration information (if available) in the Methods section.

Abstract and Proceeding Paper

These types of articles contain peer reviewed research output from conferences and can be submitted to one of MDPI’s proceedings journals: https://www.mdpi.com/about/proceedings .

Abstracts could be a short single paragraph summarizing the main topic and findings presented at the conference, or the extension of a typical abstract that contains a moderately detailed account of the work. They should be submitted to a conference in advance and provide details in support of a presentation made at the conference. The main text usually has no sections, but may include tables, figures, and references. The length should not exceed four pages.

Proceeding papers report new evidence or conclusions, and are expanded versions of work presented in a conference presentation. Conference proceedings can be incomplete findings that report on an idea, technique, or important results, thus providing readers with a brief overview of recent work or specific projects of significant interest. The structure is similar to a standard research article, and should include sections such as an Introduction, Methods, Results, Conclusions, etc. It is recommended that the length should not exceed eight pages.

All published items will be assigned a digital object identifier (DOI) and be citable, and posters, videos, or PPT presentations can be published together as the Supplementary Materials.

For updating published papers, please see the descriptions for Corrections, Retractions, Comments and Replies, and Expressions of Concern online at Research and Publication Ethics .

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Types of journal articles

It is helpful to familiarise yourself with the different types of articles published by journals. Although it may appear there are a large number of types of articles published due to the wide variety of names they are published under, most articles published are one of the following types; Original Research, Review Articles, Short reports or Letters, Case Studies, Methodologies.

Original Research:

This is the most common type of journal manuscript used to publish full reports of data from research. It may be called an  Original Article, Research Article, Research, or just  Article, depending on the journal. The Original Research format is suitable for many different fields and different types of studies. It includes full Introduction, Methods, Results, and Discussion sections.

Short reports or Letters:

These papers communicate brief reports of data from original research that editors believe will be interesting to many researchers, and that will likely stimulate further research in the field. As they are relatively short the format is useful for scientists with results that are time sensitive (for example, those in highly competitive or quickly-changing disciplines). This format often has strict length limits, so some experimental details may not be published until the authors write a full Original Research manuscript. These papers are also sometimes called Brief communications .

Review Articles:

Review Articles provide a comprehensive summary of research on a certain topic, and a perspective on the state of the field and where it is heading. They are often written by leaders in a particular discipline after invitation from the editors of a journal. Reviews are often widely read (for example, by researchers looking for a full introduction to a field) and highly cited. Reviews commonly cite approximately 100 primary research articles.

TIP: If you would like to write a Review but have not been invited by a journal, be sure to check the journal website as some journals to not consider unsolicited Reviews. If the website does not mention whether Reviews are commissioned it is wise to send a pre-submission enquiry letter to the journal editor to propose your Review manuscript before you spend time writing it.  

Case Studies:

These articles report specific instances of interesting phenomena. A goal of Case Studies is to make other researchers aware of the possibility that a specific phenomenon might occur. This type of study is often used in medicine to report the occurrence of previously unknown or emerging pathologies.

Methodologies or Methods

These articles present a new experimental method, test or procedure. The method described may either be completely new, or may offer a better version of an existing method. The article should describe a demonstrable advance on what is currently available.

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Article Review

Barbara P

Article Review - A Complete Writing Guide With Examples

Published on: Feb 17, 2020

Last updated on: Dec 19, 2022

Article Review

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An article review format is a scholarly way to analyze and evaluate the work of other experts in your specific field. Scholars or students mainly use it outside of the education system. But it's typically done for clarity, originality, and how well contributions from this expert have been made to their discipline.

When answering questions about what is an article review and how to write one, you must understand the type of analysis the instructor requires. Continue reading to get a detailed idea of writing a perfect article review in no time.

What is an Article Review?

An article review is a writing piece that summarizes and assesses someone else's article. It entails understanding the central theme of the article, supporting arguments, and implications for further research.

A review has specific guidelines and format to write. It can be either a critical review or a literature review. A critical analysis deals with a specific type of text in detail, while a literature review is a broader kind of document.

Moreover, an article review is important because of the following reasons:

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Types of Review

Below are the three main types of article reviews:

1. Journal Article Review

A journal article review is essentially a critique of an academic paper. Here, the author provides his thoughts on both strengths and weaknesses to demonstrate how it fits in with other work and what makes this publication stand out.

Check out the following example to help you understand better.

Example of Journal Article Review

2. Research Article Review

A research article review is different from a journal article review as it evaluates the research methods used in the study. It also compares them to other research studies.

Here is a sample for you to get an idea.

Example of Research Article Review

3. Science Article Review

Science article reviews involve publications in the realm of science. This type of research provides detailed background information so you can understand it in a better way.

Have a look at the below example.

Example of Science Article Review

Article Review Format

The format of your article must follow the citation style required by your professor. If you are not sure, ask him to clarify the following pointers about the preferred format. It will help you format an article review adequately.

After knowing the answers to these questions, you can start writing your article review. Here, we have mentioned the two most commonly used citation styles, APA and MLA.

1. APA Format

An article can appear in academic journals, newspapers, and websites. You need to write bibliographical entries for the sources you use when writing an APA format article review:

2. MLA Format

Here is how you cite your sources in MLA format.

How to Write an Article Review?

Students often find writing an article review for the very first time daunting. Thus, it is best to start with a few preparatory steps.

The following is a complete step-by-step guide to write an effective article review in no time

1. The Pre-Writing Process

First, you need to know the type of review you are writing as it will help while reading an article. Here are some of the main stages of this process to help you get started.

After this process, you can begin writing your own review.

2. Write the Title

First, write a title that reflects the main focus of your research work. It can be either interrogative, descriptive, or declarative.

3. Cite the Article

Next, add the citation for the article that you have reviewed. Consider the style of citation specified by your instructor. For example, if you were using MLA style, the citation would look like this:

Author’s last and first name. “The title of the article.” Journal’s title and issue(publication date): page(s). Print

Abraham John. “The World of Dreams.” Virginia Quarterly 60.2(1991): 125-67. Print.

4. Article Identification

After citing the article properly, include the identification of the reviewed article. All the information given below must be included in the first paragraph.

For Example

The report, “Poverty increases school drop-outs,” was written by Brian Faith – a Health officer – in 2000.

5. Introduction

Before you start to write, you must organize your thoughts. You can use an article review template or outline of your assignment before you start. However, if you are wondering how to start an article review, always start with writing an introduction. It should contain the following things:

6. Summarize the Article

Write the summary of the article and discuss the central arguments presented by the author. Also, make a list of relevant facts and findings and include the author's conclusion.

7. Critique It

Here, state the author’s contribution and present the strengths and weaknesses that you have found in the article. Also, make a list of research gaps and see if the facts and theories support the arguments.

8. Draft a Conclusion

This section will sum up the critical points, findings, and your critique of the article. Here, the writer should also state the accuracy and validity of the review by presenting suggestions for future research work.

9. Revise and Proofread

The last step before submitting your article review is revising and proofreading. It is an essential part of the writing process, so make sure to do it right. For this, read the review aloud to identify any spelling, grammar, punctuation, and structure mistakes.

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Article Review Outline

After reading your article, organize your thoughts in an outline. Write down important facts or contributions to the field. Also, identify the weaknesses and strengths of your publication and start to discuss them accordingly.

If your professor doesn't want a summary section, then do not write one. Like other assignments, an article review must also contain an introduction, a body, and a conclusion. So divide your outline according to these sections and subheadings in the body.

If you find that you're having trouble with prewriting and brainstorming for this assignment, try looking for a sample outline. An outline for the article review must contain the below parts:

Refer to the following template to understand outlining the article review in detail.

Article Review Format Template

Article Review Example

Here is a sample review paper for you to write your own perfectly on time.

Sample of Article Review

Law Article Review

Looking at relevant article review examples may be useful to you in the following ways:

You can learn a lot about an author's style and voice by reading selections from their work. As you can see, skimming a few samples may be really useful to you.

As a result, the best method to acquire experience writing this sort of paper is to look for an online article review example that matches your grade level.

Article Review Topics

Below you can find examples of topics for article review.

It is hard to write a good review because you need to find an article in a reliable source and read it. With this, you are also required to evaluate the information and think about any further limitations. Thus, the writer must have exceptional writing and analytical skills.

Therefore, if you are unsure about your skills, you can always get professional help online.  MyPerfectWords.com  is the  top essay writer service  that provides legit writing help at affordable rates. Our team of top writers can write papers of all types and for different academic levels and subject matters with perfection.

So, do not think much, and hire our  writing services  to get your review done within the given deadline.

Frequently Asked Questions

What is the purpose of an article review.

The main purpose of writing a review is to create an informative synthesis of the best resources available in the literature for an important research question or current area of study.

How long should an article review be?

Article reviews vary in length. Narrative reviews range between 8,000 and 40,000 words. On the other hand, systematic reviews are usually shorter and less than 10,000 words.

Barbara P (Literature, Marketing)

Dr. Barbara is a highly experienced writer and author who holds a Ph.D. degree in public health from an Ivy League school. She has worked in the medical field for many years, conducting extensive research on various health topics. Her writing has been featured in several top-tier publications.

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Types of Review Articles: The Complete List

There are a lot of different types of reviews. In this article, we are going to provide you with the 10 major types of reviews.

They include umbrella, scoping, critical, literature, realistic, integrative, mapping, rapid, and quantitative systematic review. We have discussed them below.

1. Umbrella Review

An umbrella review is the master review. The review takes evidence from already existing reviews to provide a high-level summary.

We use the umbrella review when we have several competitive interventions. The review is of great importance because it turns evidence into practice.

Apart from just determining what is known on a topic, the review also determines what remains unknown and recommendations.

These recommendations will be used to further carry out an investigation. Information on an umbrella review is most of the time presented using tables.

People who are much involved with this type of review are librarians. You could therefore approach a librarian if you need help with the umbrella review.

2. Scoping Reviews

A scoping review is also known as a scooping project. The review is used to categorize existing literature. The literature is grouped according to features, volume, and nature.

Most people confuse this review with the mapping review. The mapping review is more of questions while the scooping review is more based on topics.

The main reason we have scooping reviews is to identify nature through research. The review is best for realizing opportunities in existing literature, explaining functional definitions, and labeling the body of a research/literature.

A lot of time is used when preparing a scoping review. Also, instead of single structured research, you will need multiple structural pieces of research. The research is not as easy as other reviews.

3. Critical Reviews

A critical review will summarize and evaluate ideas and summarize reports on an article. Writers use this review to express what they already know about the subject.

Before expressing their view they need to think carefully and consider both weaknesses and strengths in what they are reviewing.

The best way to do critical reviews is by scanning the research to be informed and effectively reviewing the literature as you question the information provided in the text.

Look at the texts from various angles to be able to evaluate the theories, frameworks, and approaches in the text.

The elements of a critical review include the introduction, summary, critique (the main body), conclusion, and references.

4. Literature Reviews

 Literature reviews are writings that academically showcase knowledge and understanding of the literature on a given topic placed in a given setting.

Unlike a literature report, a literature review will evaluate essential materials. Apart from the critic’s evaluation, a literature review should also include a brief synopsis.

Although the review forms part of a research project, it can still be treated as an independent piece of work.

The purpose of having literature reviews is to establish familiarity and get to understand research on a given field before conducting a new investigation.

A literature review is the best way to summarize and analyze a theory or investigation, identify gaps that exist in research, and identify areas of controversy.

5. Realist Reviews

A realistic review can also be called a realistic synthesis. Realistic reviews are used to study interventions that are so complex to perceive the limitations of conventional methodology. It also highlights mechanisms, context, and outcomes to explain the intended or unintended differences.

Realistic reviews are crucial because they are used to unpack the impact of complex interventions as they strive to answer questions such as “under what circumstance do a given thing work” and “to who does the thing in discussion work for”.

6. Integrative Reviews

An integrative review will summarize theatrical research to give a better understanding of a given situation.

The integrative review methodology can build upon informing research, policy initiation, and nursing science.

This review accepts the inclusion of various approaches. The integrative review approach is appropriate when research is more focused on the occurrence of interest and when research supports a vast variety of inquiries.

7. Mapping Reviews

A mapping review will classify trends/themes, categorize trends/themes and characterize patterns in evidence production.

A mapping review is supposed to make you thematically understand research on a provided topic. That way, it is possible to assess gaps that could be conveyed by future research. The review is appropriate when there are lots of foregoing literature.

8. Rapid Reviews

A rapid review is a variation of structured review. The structured review can balance constraints even when considerations are corrupt.

Rapid reviews are conducted by a lot of institutions in the world. Rapid reviews can examine reports, articles, and books to compare reviews using Scoping reviews.

9. Mixed Study Review

Researchers use the mixed study review to gather and analyze qualitative and quantitative information under the same topic of study.

The mixed study review features various methods of designs that include embedded, explanatory, exploratory, and parallel designs.

The review provides answers to questions quantitative and qualitative methods cannot answer.

Mixed study reviews can also enrich the researchers’ experience by illuminating issues of study.

10. Quantitative Systematic Reviews

Quantitative Systematic Review is of much use in nursing research. To reduce biases and make the review more trustworthy, reviews based on protocol should be used.

That way, reproducibility, and transparency shall be enhanced. Developing quantitative systematic reviews is not hard, the only thing that limits it is inadequate resources.

A quantitative systematic review aims to guide researchers as they develop systematic review protocols.  

Apart from helping researchers develop review protocol, this review also helps them enhance trustworthiness and realize the importance of completing quantitative systematic findings.

Since this review is useful in clinical practices, it is important to base it on the planned protocol. That way trustworthiness will also be enhanced.

Everything that appears on the quantitative systematic review should be outlined in detail processes used to undertake the review.

Some of these details include inclusion, exclusion criteria, and main focus search terms. The method used for data extraction, data analysis, and critical appraisal should also be included to make sure there is transparency.

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review articles types

Types of Article Reviews: Formats and Tips for Writing

15 Jul 2021

Quick Navigation

❓What is an Article Review?

✒️Types of Article Reviews

📑Outline of an Article Review

✍️Formatting University Papers

✅Writing Tips for an Article Review

An article review is one of the main ways to analyze and estimate the written works of specialists from various spheres. Its main task is to evaluate how the work is written on the topic, whether it is original and whether the author has contributed innovative ideas to his field of occupation. In addition, this type of paper can be used in the educational process and to assess certain materials in work or everyday life.

When writing any task, you should know how to proceed and structure your document appropriately. That is why, if you need to write an article review, read our analysis of the main postulates of this type of work to complete this task as quickly and efficiently as possible.

What is an Article Review?

An article review is an evaluation of the literature. It includes a summary, analysis, and comparison. Such academic tasks teach students to work in different fields, analyze essays written by experts, and improve writing skills. This type of academic assignment does not present new information. A student has to respond to already existing knowledge.

Different types of review articles require in-depth research and time to find decent arguments. A student must clearly understand the topic by discussing theories, ideas, and research. An essay has a particular structure and must be formatted according to the requirements.

There are several types of assignments: narrative, evidence, and systematic. Follow the guide to create these three types of academic studies. Learn how to structure and format an essay with the help of a professional article writing service or get an essay written by an experienced tutor.

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What Types of Article Reviews Exist?

There are three main types of review articles that you can be asked to write during a college course:

Different types of articles are united by providing your understanding of the topic. Create an informative title to grab the readers' attention. The title has to be short but concise. Include information about the methods and ideas. Follow the structure of an essay and format it.

Article Review Outline

All types of article review require to be written following a particular plan. It makes the process of analysis and evaluation of a specific paper a lot easier for writers. To compose your article professionally, stick to the outline of seven steps.

Following this scheme, you will get an excellent review writing without wasting dozens of hours understanding how to do it properly. And your readers will appreciate the clarity and informativeness of your paper!

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Formatting Papers for a University

Most academic papers have to be formatted in APA or MLA style. These are the two required formats at universities for all types of review article. Articles are published in journals, newspapers, or on websites. We will show you two essential types of reviews. Check the example of an APA type of review and MLA article review format below:

Journal article

Look at this example:

Taormina Robert J. and Gao Jennifer H. 2013. Maslow and the Motivation Hierarchy: Measuring Satisfaction of the Needs. The American Journal of Psychology. Vol.126, No. 2, pp.155-177pp.

For instance,

Burgess Robert L. “A Differencial Association-Reinforcement Theory of Criminal Behavior”. Oxford University Press, Vol.14, 1966, pp.128-147pp.

Newspaper article review format

Here is the example:

LaFraniere Sharon. 2022, November, 14. Moderna Says New Covid Booster Strenthens Immune Response Against Subvariants. The New Yourk Times. pp.1-4pp.

As an instance:

Longman Jeré D. “In Their First Loss, the Eagles Score Early and Then Slumber.” The New York TImes. 15 November 2022. pp.6-7pp. Print.

Website article

For instance:

McKenzie P. J. 2022, November, 16. Scientists say harassment in the Antarctic must stop - but US plan falls short. Retrieved from https://www.nature.com/articles/d41586-022-03723-3
Rejcek Peter. “Italian researches discover new recipe for exctenting shelf life of fresh pasta by 30 days.” Frontiers Science News. Frontiers Science Communications, 2, November, 2022.blog.frontiersin.org/2022/11/02/frontiers-microbiology-fresh-pasta-probiotics/. 16 November 2022.

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Tips for Writing an Article Review

A review of paper articles is a complicated task given to higher degree-level students. If you have to write this academic assignment, the most valuable advice is to leave as much time as possible. You will have to learn and write it from scratch.

Choose one topic and concentrate on it. Sometimes, a review requires studying several methods and ideas. If you can choose the topic yourself, pick the one that interests you

Create a thesis for your assignment

Summarize all the key points retrieved from the author's paper and write them down

Evaluate your own opinion of the author's methods and ideas. All arguments have to be decent and supported by references

Annotate the chosen sources in your essay. Choose five or more sources that helped you evaluate your own opinion about the author's idea

Follow the basic structure of an academic assignment: the introduction, body, and conclusion. Some review article types may include more paragraphs

Discuss whether the author is right or wrong. Admit and disagree with the author's thoughts by providing evidence from your research

Critique the author's paper by detecting unanswered questions, contradictions, or disparities

Check, edit, and improve the review. Make sure there are no grammar errors. Make your homework informative, clear, and engaging. Conduct research in advance to provide an exciting essay. Cite your article and add references found by you

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Such writing companies provide academic papers for students of all education levels. Buy a paper free of errors and plagiarism online. With an outstanding article review, you will impress your teacher and get praise.

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What is a review article?

Learn how to write a review article.

What is a review article? A review article can also be called a literature review, or a review of literature. It is a survey of previously published research on a topic. It should give an overview of current thinking on the topic. And, unlike an original research article, it will not present new experimental results.

Writing a review of literature is to provide a critical evaluation of the data available from existing studies. Review articles can identify potential research areas to explore next, and sometimes they will draw new conclusions from the existing data.

Why write a review article?

To provide a comprehensive foundation on a topic.

To explain the current state of knowledge.

To identify gaps in existing studies for potential future research.

To highlight the main methodologies and research techniques.

Did you know? 

There are some journals that only publish review articles, and others that do not accept them.

Make sure you check the  aims and scope  of the journal you’d like to publish in to find out if it’s the right place for your review article.

How to write a review article

Below are 8 key items to consider when you begin writing your review article.

Check the journal’s aims and scope

Make sure you have read the aims and scope for the journal you are submitting to and follow them closely. Different journals accept different types of articles and not all will accept review articles, so it’s important to check this before you start writing.

Define your scope

Define the scope of your review article and the research question you’ll be answering, making sure your article contributes something new to the field. 

As award-winning author Angus Crake told us, you’ll also need to “define the scope of your review so that it is manageable, not too large or small; it may be necessary to focus on recent advances if the field is well established.” 

Finding sources to evaluate

When finding sources to evaluate, Angus Crake says it’s critical that you “use multiple search engines/databases so you don’t miss any important ones.” 

For finding studies for a systematic review in medical sciences,  read advice from NCBI . 

Writing your title, abstract and keywords

Spend time writing an effective title, abstract and keywords. This will help maximize the visibility of your article online, making sure the right readers find your research. Your title and abstract should be clear, concise, accurate, and informative. 

For more information and guidance on getting these right, read our guide to writing a good abstract and title  and our  researcher’s guide to search engine optimization . 

Introduce the topic

Does a literature review need an introduction? Yes, always start with an overview of the topic and give some context, explaining why a review of the topic is necessary. Gather research to inform your introduction and make it broad enough to reach out to a large audience of non-specialists. This will help maximize its wider relevance and impact. 

Don’t make your introduction too long. Divide the review into sections of a suitable length to allow key points to be identified more easily.

Include critical discussion

Make sure you present a critical discussion, not just a descriptive summary of the topic. If there is contradictory research in your area of focus, make sure to include an element of debate and present both sides of the argument. You can also use your review paper to resolve conflict between contradictory studies.

What researchers say

Angus Crake, researcher

As part of your conclusion, include making suggestions for future research on the topic. Focus on the goal to communicate what you understood and what unknowns still remains.

Use a critical friend

Always perform a final spell and grammar check of your article before submission. 

You may want to ask a critical friend or colleague to give their feedback before you submit. If English is not your first language, think about using a language-polishing service.

Find out more about how  Taylor & Francis Editing Services can help improve your manuscript before you submit.

What is the difference between a research article and a review article?

Before you submit your review article….

Complete this checklist before you submit your review article:

Have you checked the journal’s aims and scope?

Have you defined the scope of your article?

Did you use multiple search engines to find sources to evaluate?

Have you written a descriptive title and abstract using keywords?

Did you start with an overview of the topic?

Have you presented a critical discussion?

Have you included future suggestions for research in your conclusion?

Have you asked a friend to do a final spell and grammar check?

review articles types

Expert help for your manuscript

review articles types

Taylor & Francis Editing Services  offers a full range of pre-submission manuscript preparation services to help you improve the quality of your manuscript and submit with confidence.

Related resources

How to edit your paper

Writing a scientific literature review

Types of Sources - What's the Difference

Comparison of Article Types

Characteristics of General Interest Articles

A black line illustration of a to-go coffee cup

What is the purpose? Provides information to a general, educated audience

Why use them? Stay up-to-date on current events and issues; Find potential research topics

Who is it for? For a broad readership ranging from high-school educated to company executives to university presidents

Who writes the article? Often written by journalists or staff writers

Who reviews the article? Articles have minimal review by editorial staff

What type of language or writing is used? Common language aimed at a high school reading level; little use of formal language, jargon, or unique terminology

Are other sources and cited? Occasionally sources are referenced in the article but rarely formated as a bibliography or footnotes

Are images and advertising included? Very often photographs, illustrations, and graphs are used to enhance an article; heavy reliance on advertising that appeals to a broad readership

How often are issues of articles published? Varies greatly and can range from daily to weekly to monthly

A general interest magazine is a periodical that contains articles written by professional writers and journalists. While these writers may have some expertise on the subject they are writing about, they are not scholars. Because these articles are written for a broad educated audience, they are usually easier to understand than articles in scholarly journals. Before they are published, these articles are also reviewed, but not by scholars. Rather, they are reviewed by professional editors working for the magazine, who may or may not have some expertise on the subject of the article.

Characteristics of Scholarly Articles

A black and white clipart graduation cap

What is the purpose? To inform, report, and show original research, experimentation, and thought

Why use them? To support your own research, opinion, hypothesis, writing, etc.

Who is it for? The reader is assumed to have a similar scholarly background

Who writes the article? Written by researchers and scholars

Who reviews the article? Articles go through strict review process by peers within the discipline / subject

What type of language or writing is used? These articles rely heavily on unique terminology, jargon, and language specific to the discipline

Are other sources and cited? Sources are always cited as footnotes, endnotes, or reference lists (bibliographies)

Are images and advertising included? Graphs, charts, and illustrations related to the research are used; typically no advertising but when used it is very selective

How often are issues of articles published? Varies greatly and can range from monthly to bi-monthly to quarterly

A scholarly journal, sometimes called a research journal, is a periodical that contains articles written by scholars and experts in a particular subject field. Your professors are scholars in the discipline they teach. Because these articles are written by experts for other experts, they contain technical and specialized vocabulary (jargon). A scholar prepares an article and submits it to a journal. A review process, known as “peer review,” requires submitted articles to be reviewed by other scholarly peers (or equals) to determine if an article is published. When it works properly, the peer review process should ensure that only high-quality articles are published in a journal.

Anatomy of a Scholarly Article

Click on the bubbles below to learn about the different parts of a scholarly article:

Characteristics of Trade / Professional Articles

A clipart image of a non-gendered person sitting at desk with a computer.

What is the purpose? Provides news and trends in a field, but not original research; showcases leaders in the field

Why use them? Stay up-to-date on trends, breakthroughs, and mover-&-shakers within a field; useful for job hunting or interviewing

Who is it for? Written for practicing professionals in almost any field or industry

Who writes the article? Written by industry professionals and experts

Who reviews the article? While reviewed by editorial staff, they are rarely peer-reviwed

What type of language or writing is used? Uses jargon or terminology specific to the field or industry

Are other sources used and cited? Sources are often mentioned within an article but not typically formated as a bibliography or footnotes

Are images and advertising included? Illustrations, charts, graphs, photographs and sometimes graphic art that is relevant to article; advertising aimed specifically to profession or industry

A trade publication is somewhere between a scholarly journal and a popular magazine. Articles in trade journals are written by and for people working in a certain field or discipline, for example, grocers, nurses, teachers, or business administrators. Article authors typically have some specialized knowledge, but are not scholars. Articles in trade publications are often easier to understand than articles in scholarly journals but are focused towards a specific group of people resulting in some use of professional terminology. Like articles in popular magazines, articles in trade journals are usually reviewed by professional editors.

Characteristics of Newspaper Articles

A clipart line drawing image of a newspaper. It doesn't look much like a real newspaper.

What is the purpose? Provides current local and international news and special interest topics like travel, lifestyle, book & movie reviews, etc.

Why use them? Stay up-to-date on what is happening in your community, the country, and world

Who is it for? Written for a general audience

Who writes the article? Written by staff reporters and columnists

Who reviews the article? Reviewed by editorial staff and not peer-reviwed

What type of language or writing is used? Uses general, everyday language and written for an 11th-grade reading level

Are other sources used and cited? Sources are often mentioned within an article but news articles do not include a bibliography or footnotes

Are images and advertising included? Illustrations, charts, graphs, photographs and sometimes graphic art that is relevant to article; advertising aimed to a general audience

How often are issues of articles published? Varies; most often daily

Popular magazines

An image of a People Magazine cover with Hillary Clinton on the cover.

Sensational magazines

review articles types

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Review Articles

review articles types

Pathogenesis, epidemiology and control of Group A Streptococcus infection

In this Review, Brouwer et al. summarize recent developments in our understanding of Group A Streptococcus (GAS), focusing on the epidemiologic and clinical features of GAS infection and the molecular mechanisms associated with GAS virulence and drug resistance.

review articles types

Surveying membrane landscapes: a new look at the bacterial cell surface

In this Review, Lithgow and colleagues explore how imaging of the bacterial cell surface at nanoscale has revealed distinct zones and specific features, including functionally defined assembly precincts for protein insertion into the membrane and equivalent lipid-assembly precincts suggested from discrete lipopolysaccharide patches.

review articles types

Intracellular lifestyle of Chlamydia trachomatis and host–pathogen interactions

In this Review, Stelzner, Vollmuth and Rudel summarize current knowledge of Chlamydia trachomatis intracellular replication, its metabolism within the host cell and how it defends against host cell autonomous and innate immune responses, as well as its transition to a persistence state.

review articles types

Staphylococcus aureus host interactions and adaptation

In this Review, Howden and co-workers examine and integrate recent key advances in understanding the mechanisms that Staphylococcus aureus uses to cause infections.

review articles types

SARS-CoV-2 variant biology: immune escape, transmission and fitness

In this Review, the authors summarize the mutations harboured by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern. They describe the impact of mutations on virus infectivity and transmissibility, and discuss SARS-CoV-2 evolution in the context of T cells, innate immunity and population immunity.

review articles types

Long COVID: major findings, mechanisms and recommendations

Long COVID is an often debilitating illness of severe symptoms that can develop during or following COVID-19. In this Review, Davis, McCorkell, Vogel and Topol explore our knowledge of long COVID and highlight key findings, including potential mechanisms, the overlap with other conditions and potential treatments. They also discuss challenges and recommendations for long COVID research and care.

review articles types

Innate immune evasion strategies of SARS-CoV-2

In this Review, Minkoff and tenOever examine the relationship between SARS-CoV-2 biology and innate immunity, and they explore how antagonism and dysregulation of host innate immune defences contribute to COVID-19 disease severity.

review articles types

Microbiota-mediated colonization resistance: mechanisms and regulation

In this Review, Caballero-Flores, Pickard and Núñez explore how the microbiota limits colonization by pathogens and the strategies used by pathogens to counter colonization resistance.

review articles types

A molecular understanding of alphavirus entry and antibody protection

In this Review, Kim and Diamond highlight recent advances in our understanding of the host factors required for alphavirus entry, the mechanisms of action by which protective antibodies inhibit different steps in the alphavirus infection cycle and candidate alphavirus vaccines currently under clinical evaluation.

review articles types

SARS-CoV-2 viral load and shedding kinetics

A better understanding of the transmission of SARS-CoV-2 is essential to inform public health measures. In this Review, Puhach, Meyer and Eckerle explore insights into what influences SARS-CoV-2 shedding, how this drives transmission and the tools available to measure this and determine infectiousness.

review articles types

Trichoderma : a multipurpose, plant-beneficial microorganism for eco-sustainable agriculture

This Review discusses the ecophysiology and diversity of Trichoderma and the complexity of its relationships in the agroecosystem environment. Considerations are also presented on how to advance Trichoderma applications in real-world scenarios, contributing towards eco-sustainable agriculture.

review articles types

Molecular mechanisms of antibiotic resistance revisited

In this Review, Blair, Webber and colleagues explore our understanding of the mechanisms of antibiotic resistance, including reduced permeability, antibiotic efflux, modification or alteration of the antibiotic target, modification or destruction of the drug itself, and bypass of metabolic pathways. They also discuss how this information can aid in developing the next generation of antimicrobial therapies.

review articles types

The dynamic lung microbiome in health and disease

Like the gut, the lung harbours a diverse, interacting assortment of microbiota. In this review, Natalini, Singh and Segal examine the role of the lung microbiome in health and disease and discuss future work that is needed to produce novel diagnostic and therapeutic tools aimed at improving lung health.

review articles types

Shaping bacterial gene expression by physiological and proteome allocation constraints

In this Review, Scott and Hwa describe how physiological constraints are sensed through metabolic fluxes and how flux-controlled regulation gives rise to simple empirical relations between protein levels and the rate of cell growth.

review articles types

Soil viral diversity, ecology and climate change

Soil viruses are highly abundant and have important roles in the regulation of host dynamics and soil ecology. In this Review, Jansson and Wu explore our current understanding of soil viral diversity and ecology, and how climate change (such as extended and extreme drought events or more flooding and altered precipitation patterns) is influencing soil viruses.

review articles types

SARS-CoV-2 variant evasion of monoclonal antibodies based on in vitro studies

In this Review, Carabelli, Robertson and colleagues explore data on the neutralization of globally circulating variants of concern by monoclonal antibodies (mAbs) and discuss how knowledge of the dynamics of viral evasion of mAbs can contribute to viral surveillance and the development of novel mAb treatments, as well as inform predictions of resistance that may arise in the future.

review articles types

Architecture of the dynamic fungal cell wall

In this Review, Gow and Lenardon describe how fungal cell walls are organized, focusing on the underlying architectural and mechanical principles that are required to deliver differing and bespoke biochemical and biophysical attributes.

review articles types

The effects of the COVID-19 pandemic on community respiratory virus activity

The COVID-19 pandemic has had a considerable impact on respiratory virus infections worldwide. In this Review, Chu and colleagues discuss the changes in community spread and consequent infections by respiratory viruses other than severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) throughout the course of the pandemic, and describe the impact on the evolution and genetic diversity of these viruses.

review articles types

Bile acids and the gut microbiota: metabolic interactions and impacts on disease

The gut microbiota metabolizes bile acids, thereby influencing human health and diseases including obesity, colitis and cancer. In this Review, Patterson and colleagues discuss host–microbiota interactions and their influence on the bile acid pool as well as therapeutic implications.

review articles types

Impact of enteric bacterial infections at and beyond the epithelial barrier

In this Review, Rogers, Mileto and Lyras explore the impact of enteric bacterial infections at and beyond the epithelial barrier. They highlight how different bacterial pathogens disrupt structural first line defences of the gut, the influence this has on the systemic dissemination of gut contents, the acute inflammatory processes that are triggered and the collective implication of these events on the regeneration of efficient barrier functions.

Quick links

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UMSN Global Nursing | Information Resource Toolkit

Characteristics of Scholarly vs. Non-Scholarly ("Popular") Sources

Peer review in 3 minutes.

How do articles get peer reviewed? What role does peer review play in scholarly research and publication? This video will explain.

Credit: North Caroline State University Libraries

More about Scholarly Article Content Types

Empirical research articles.

Start by reading the article abstract. Does the author talk about their data and methodology?

Look at the article itself. Most will follow a particular structure:

Example: Burgard, Sarah A. and Jennifer A. Ailshire. 2013. “ Gender and Time for Sleep among U.S. Adults .” American Sociological Review 78(1):51–69.

Literature Review Articles

Start by reading the abstract. Does the author talk about gathering literature and reviewing existing studies?

You can use a review article in your reference list to talk about the overall trends and findings on your topic. 

Example: Sampson, Robert J., Jeffrey D. Morenoff, and Thomas Gannon-Rowley. 2002. “ Assessing ‘Neighborhood Effects’: Social Processes and New Directions in Research .” Annual Review of Sociology 28(1):443–78.

Theoretical Articles

Example: Jansen, Robert S. 2011. “ Populist Mobilization: A New Theoretical Approach to Populism .” Sociological Theory 29(2):75–96.

Other Scholarly Article Types

Other types of articles may also be published in the scholarly literature such as:

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here .

What We Publish

Research articles.

Research Articles present the results of original research that address a clearly defined research question and contribute to the body of academic knowledge.

PLOS ONE  considers Research Articles in all areas of the natural sciences, medicine, and engineering, as well as the related social sciences and humanities.

In keeping with our mission to publish all methodologically and ethically rigorous research, we will consider Research Articles reporting negative and null results.

Research Articles typically consist of the following headings:

Submitted Research Articles are evaluated against the PLOS ONE criteria for publication and should also adhere to the author submission guidelines .

Articles reporting new methods

PLOS ONE  considers Research Article submissions which report new methods, software, databases and tools as the primary focus of the article. These should also adhere to the utility, availability and validation criteria in the  guidelines for specific study types .

Systematic reviews and meta-analyses

PLOS ONE  considers Research Article submissions which report systematic reviews and meta-analyses: reviews of a clearly formulated research question that use explicit, systematic methods to identify, select, and critically appraise relevant research, and to collect and analyze data from the included studies. For more information see our submissions guidelines for systematic reviews and meta-analyses .

Clinical Trials

Clinical Trials report the results of studies in which participants are prospectively assigned to a health-related intervention in order to evaluate the effects on health outcomes.  PLOS ONE  assesses Clinical Trials manuscripts against the same  publication criteria  as Research Articles, but they must also meet the additional requirements outlined in the  submissions guidelines for Clinical Trials .

Lab Protocols

Lab Protocols are peer-reviewed articles comprising detailed step-by-step descriptions of experimental and computational techniques. Lab Protocols have been developed as part of a  partnership between PLOS and protocols.io , a dedicated platform for developing and sharing reproducible methods, and consist of:

PLOS ONE  considers Lab Protocols submissions in all areas of the journal  scope . For more information on submissions requirements and evaluation criteria see  the Lab Protocols submission guidelines .

Study Protocols

Study Protocols describe detailed plans for conducting research, including the background, rationale, objectives, methodology, statistical plan, and organization of a research project.  PLOS ONE  accepts submissions of Study Protocols for any study type within the journal’s scope.

Read the Study Protocols submission guidelines for more information about submission requirements and evaluation criteria.

Registered Reports

Registered Reports are research articles that undergo peer review at the study design or protocol stage, prior to conducting experiments, data collection or analysis. The Registered Report format aims to support a strong methodological approach, increase the reproducibility of results, and address publication bias.  Read more on our blog .

Assessment takes place in two stages and results in two linked publications:

Scope and submission requirements for Registered Report Protocols and Registered Reports are similar to those for a regular research article submission. Read the  Registered Report Protocol and Registered Report submission guidelines  for more.

Commissioned Article Types

PLOS ONE does not consider unsolicited submissions of the article types below - these articles must be commissioned or invited by the PLOS ONE editors, or, in the case of Collection Reviews and Collection Overviews, by Guest Editors of Collection partners.

Collection Reviews

PLOS ONE  considers Collection Review articles within pre-planned  Collections  with the goal to provide deeper insight into one or more of the topics covered in the Collection. These articles are compelling narrative reviews that discuss current developments in a particular field under the Collection’s scope and draw meaningful conclusions adding to knowledge in the field. They should be balanced, coherent, representative of the literature on the topic covered, and clearly positioned in the subject of the Collection.

PLOS ONE  staff editors will not consider unsolicited Collection Reviews. Collection Reviews will be considered within a pre-planned Collection subject to prior approval by journal editors, or they may be commissioned by staff editors.  PLOS ONE  staff editors will not consider unsolicited Collection Reviews. Collection Reviews should include:

Collection Overviews

PLOS ONE  considers Collection Overview articles within planned Collections. Collection Overviews discuss the relevant history and scientific background of a Collection, and place the articles included in the Collection within the context of knowledge in the field.

PLOS ONE  staff editors do not consider unsolicited Collection Overviews. Collection Overviews will instead be commissioned by Guest Editors or Collection partners, or may be commissioned by staff editors.

Formal Comments

Formal Comments are invited by  PLOS ONE  editors to promote scientific discourse about  PLOS ONE  articles. They provide additional perspectives or context on a publication, especially in areas of policy, societal relevance, or ongoing scientific debate.

PLOS ONE  may invite a Formal Comment as:

Formal Comments should be concise, coherent, well-argued and of timely relevance to the field. Formal Comments undergo peer review, and the journal may also invite the authors of the article under discussion to provide a signed review or to submit a response to the Formal Comment.  PLOS ONE  editors do not consider unsolicited Formal Comments.

Formal Comments are not meant to address concerns around publication ethics. Direct ethics concerns about PLOS ONE  to the PLOS Publication Ethics team​ and cc the journal .

Topic Pages

Topic Page articles are intended to increase the coverage of scientific topics in Wikipedia. Topic Pages are written in the style of a Wikipedia article and, after open peer review on the  PLOS Wiki , become a published copy of record with a dynamic version of the article posted on Wikipedia.

While Academic Editors most often solicit Topic Pages from researchers in their areas of expertise, we also welcome new proposals and inquiries for editorial consideration. Proposals should address topics that are of interest to the scientific community and wider general public and that are not yet covered or are currently under-developed, in Wikipedia.To propose a Topic Page, please contact our editorial office at [email protected] .

Post-Publication Notices

PLOS publishes Corrections, Expressions of Concern, and Retraction notices, as needed, to address issues that arise after a PLOS article has been published.

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Review: Chris Rock’s ‘Selective Outrage’ Strikes Back

A year after Will Smith slapped him at the Oscars, Rock responded fiercely in a new stand-up special, Netflix’s first experiment in live entertainment.

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Chris Rock, wearing a white dress shirt, holds a microphone close to his face.

By Jason Zinoman

One year later, Chris Rock slapped back. Hard.

It was certainly not as startling as Will Smith hitting him at the Oscars, but his long-awaited response, in his new Netflix stand-up special “ Selective Outrage ” on Saturday night, had moments that felt as emotional, messy and fierce. It was the least rehearsed, most riveting material in an uneven hour.

Near the end, Rock even botched a key part of one joke, getting a title of a movie wrong. Normally, such an error would have been edited out, but since this was the first live global event in the history of Netflix, Rock could only stop, call attention to it and tell the joke again. It messed up his momentum, but the trade-off might have been worth it, since the flub added an electric spontaneity and unpredictability that was a drawing card.

At 58, Rock is one of our greatest stand-ups, a perfectionist whose material, once it appeared in a special, always displayed a meticulous sense of control. He lost it here, purposely, flashing anger as he insulted Smith , offering a theory of the case of what really happened at the Academy Awards after he made a joke about Jada Pinkett Smith’s hair, and in what will be the most controversial part of the set, laid much of the blame on her. This felt like comedy as revenge. Rock said he long loved Will Smith. “And now,” he added, pausing before referencing the new movie in which Smith plays an enslaved man, “I watch ‘Emancipation’ just to see him get whooped.”

One of the reasons Netflix remains the leading stand-up platform has been its ability to create attention-getting events. No other streamer comes close. Through a combination of razzle dazzle and Rolodex spinning, the streaming service packaged this special more like a major sporting event than a special, a star-studded warm-up act to the Oscars next week.

It began with an awkward preshow hosted by Ronny Chieng, who soldiered through by poking fun at the marketing around him. “We’re doing a comedy show on Saturday night — live,” he said, before sarcastically marveling at this “revolutionary” innovation. An all-star team of comics (Ali Wong, Leslie Jones, Jerry Seinfeld), actors (Matthew McConaughey) and music stars (Paul McCartney, Ice-T) hyped up the proceedings, featuring enough earnest tributes for a lifetime achievement award. As if this weren’t enough puffery, Netflix had the comedians Dana Carvey and David Spade host a panel of more celebrations posing as post-show analysis.

This was unnecessary, since Netflix already had our attention by having Rock signed to do a special right after he was on the receiving end of one of the most notorious bad reviews of a joke in the history of television. Countless people weighed in on the slap, most recently the actor and comic Marlon Wayans, whose surprisingly empathetic new special, “God Loves Me,” is an entire hour about the incident from someone who knows all the participants. HBO Max releasing that in the last week was its own counterprogramming.

Until now, Rock has said relatively little about the Oscars, telling a few jokes on tour, which invariably got reported in the press. I’m guessing part of the reason he wanted this special to air live was to hold onto an element of surprise. Rock famously said that he always believed a special should be special. And he has done so in previous shows by moving his comedy in a more personal direction. “Tamborine,” an artful, intimate production shot at the BAM Harvey theater, focused on his divorce. This one, shot in Baltimore, had a grander, more old-fashioned vibe, with reaction shots alternating with him pacing the stage in his signature commanding cadence.

Dressed all in white, his T-shirt and jeans hanging loosely off a lanky frame, and wearing a shiny bracelet and necklace with the Prince symbol, Rock started slowly with familiar bits about easily bruised modern sensibilities, the hollowness of social media and woke signaling. He skewered the preening of companies like Lululemon that market their lack of racism while charging $100 for yoga pants. Most people, he says, would “prefer $20 racist yoga pants.”

If there’s one consistent thread through Rock’s entire career, it’s following the money, how economics motivates even love and social issues. On abortion, he finds his way to the financial angle, advising women: “If you have to pay for your own abortion, you should have an abortion.”

A commanding theater performer who sets up bits as well as anyone, Rock picked up momentum midway through, while always hinting at the Smith material to come, with a reoccurring refrain of poking fun at Snoop Dogg and Jay-Z before making clear it’s just for fun: “Last thing I need is another mad rapper.” Another running theme is his contempt for victimhood. His jokes about Meghan Markle are very funny, mocking her surprise that the royal family is racist, terming them its originators, the “Sugarhill Gang of racism.”

On tour, his few jokes about Smith were once tied to his points about victimhood. But here, he follows one of his most polished and funny jokes, comparing the dating prospects of Jay-Z and Beyoncé if they weren’t stars but worked at Burger King, with a long, sustained section on the Oscars that closes the show. Here, he offers his theory on Will Smith, which is essentially that the slap was an act of displacement, shifting his anger from his wife cheating on him and broadcasting it onto Rock. The comic says his joke was never really the issue. “She hurt him way more than he hurt me,” Rock said, using his considerable powers of description to describe the humiliation of Smith in a manner that seemed designed to do it again.

There’s a comic nastiness to Rock’s insults, some of which is studied, but other times appeared to be the product of his own bottled-up anger. In this special, Rock seemed more raw than usual, sloppier, cursing more often and less precisely. This was a side of him you hadn’t seen before. The way his fury became directed at Pinkett Smith makes you wonder if this was also a kind of displacement. Going back into the weeds of Oscar history, Rock traced his conflict with her and Smith to when he said she wanted Rock to quit as Oscar host in 2016 because Smith was not nominated for the movie “ Concussion ” (the title that he mangled).

That her boycotting that year’s Oscars was part of a larger protest against the Academy for not nominating Black artists went unsaid, implying it was merely a pretext. Rock often establishes his arguments with the deftness and nuance of a skilled trial lawyer, but he’s not trying to give a fair, fleshed out version of events. He’s out for blood. There’s a coldness here that is bracing. Describing his jokes about Smith’s wife at the ceremony in 2016, he put it bluntly: “She started it. I finished it.” But, of course, as would become obvious years later, he didn’t.

Did he finish it in this special? We’ll see, but I think we’re in for another cycle of discourse as we head into the Academy Awards next week.

At one point, Rock said there are four ways people can get attention in our culture: “Showing your ass,” being infamous, being excellent or playing the victim. It’s a good list, but this special demonstrates a conspicuous omission: Nothing draws a crowd like a fight.

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Original research article, high serum levels of the c-propetide of type v collagen (pro-c5) are prognostic for short overall survival in patients with pancreatic ductal adenocarcinoma.

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Introduction: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a pronounced fibrotic tumor microenvironment, which impairs treatment response. Type I and V collagens are responsible for the densely packed fibrils in the tumor fibrosis environment. While the role of the major type I collagen in cancer is well described, less is known about the minor type V collagen. Quantifying collagen propeptides in serum has been shown to have prognostic and predictive value. In this study, we evaluated the clinical utility of measuring the propeptide of type V collagen (PRO-C5) in serum from a discovery cohort and a validation cohort of patients with PDAC as well as in non-pancreatic solid tumor types to explore the relevance of the PRO-C5 biomarker in cancer.

Methods: Serum PRO-C5 was measured in three cohorts: a discovery cohort (19 healthy controls, 12 patients with chronic pancreatitis and 33 patients with PDAC (stage I-IV)), a validation cohort (800 patients with PDAC (stage I-IV)), and a non-pancreatic solid tumor type cohort of 33 healthy controls and 200 patients with 10 different non-pancreatic solid tumor types. The levels of serum PRO-C5 in patients with cancer were compared to levels in healthy controls. The association between PRO-C5 levels and overall survival (OS) was evaluated in patients with PDAC after adjusting for established prognostic factors.

Results: PRO-C5 was significantly increased in serum from patients with PDAC compared to healthy controls ( p < 0.001). High PRO-C5 levels were significantly associated with short OS in both the discovery- and the validation cohort, especially in early stages of PDAC (validation cohort stage II, HR = 2.0, 95%CI1.2-3.4). The association was independent of other prognostic parameters including stage, performance status and CA19-9. Furthermore, serum levels of PRO-C5 were significantly increased in serum from patients with other non-pancreatic solid tumor types compared to healthy controls.

Conclusion: High levels of serum PRO-C5 is prognostic for short OS in patients with PDAC and may provide clinical value in many other tumor types beyond PDAC. This underlines the importance of type V collagen in tumor fibrosis. PRO-C5 could have the potential to be used in several aspects within drug discovery, patient stratification and drug efficacy.

1 Introduction

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease as only 20% of the patients have resectable disease ( McGuigan et al., 2018 ; Klein, 2019 ; Khalaf et al., 2021 ; Siegel et al., 2021 ). The remaining patients can only be offered palliative oncologic treatment or best supportive care ( McGuigan et al., 2018 ). However, there is a high degree of treatment resistance to oncologic treatment. One explanation is an extremely fibrotic PDAC tumor microenvironment. Tumor fibrosis cause increased interstitial pressure, which in turn reduces drug delivery ( Heldin et al., 2004 ; Thomas and Radhakrishnan, 2019 ). In addition, tumor fibrosis inhibits T-cell activity and migration, which results in diminished efficacy of immunotherapy ( Mariathasan et al., 2018 ; Chen et al., 2021 ; Ogawa et al., 2021 ; Grout et al., 2022 ; Lander et al., 2022 ). Therefore, there is a high need for novel strategies to overcome tumor fibrosis in the treatment of patients with PDAC and consequently to identify tumors with high fibrotic activity.

Tumor fibrosis is characterized by an augmented activity of cancer-associated fibroblasts (CAFs), responsible for an abnormal extracellular matrix (ECM) remodeling ( Nissen et al., 2019 ). The CAF-mediated ECM remodeling results in degradation of existing collagen fibers that are replaced by new and more densely packed collagen fibers, creating a stromal barrier surrounding the tumor cells ( Nissen et al., 2019 ) ( Winkler et al., 2020 ). Type I collagen is the most abundant CAF-derived fibrillar collagen and a major component of the collagen fibers that play important roles during tumor progression ( Menke et al., 2001 ; Armstrong et al., 2004 ; Cheng and Leung, 2011 ; Gao et al., 2016 ; Barcus et al., 2017 ; Chen et al., 2022 ). The pathogenic phenotype of CAFs was originally thought to derive from the ability to produce large quantities of collagen, but recent studies focusing on type I collagen have emphasized the importance of the collagen quality and fiber architecture, as a central component in its tumorigenic capacity ( Chen et al., 2022 ; Su et al., 2022 ). Interestingly, the minor fibrillar type V collagen has been suggested to be a key regulator of type I collagen architecture.

Type V collagen has many roles in the healthy ECM, as it binds to different ECM proteins such as other collagens, TGF-β, elastin and metalloproteinases, thereby modulating cellular behavior ( Symoens et al., 2010 ). The most abundant isoform of type V collagen consist of two α1 chains and one α2 chain that forms a heterotrimer. In healthy tissue, type I and V collagen have a very close relationship, as the two collagens copolymerize into heterotypic fibrils ( Wenstrup et al., 2004 ; Aszódi et al., 2006 ; Sun et al., 2011 ) ( Figure 1 ). The binding of type V collagen to type I collagen is important for structural integrity and deficiency of type V collagen results in disorders like Ehlers-Danlos syndrome and corneal disease, which are characterized by abnormal collagen fibrils ( Mak et al., 2016 ). Type V collagen deficient mice (COL5a1 −/− ) embryos die already at day 10.5 as they also lack type I collagen fibrils. Moreover, heterozygous type V collagen mice (COL5a1 −/+ ) survive, but show 50% decrease in collagen content and fibrillar density ( Wenstrup et al., 2004 ). Thus, the binding between type V and I collagen results in a homeostatic fibril structure and tissue architecture. However, a complete understanding of its role in tumor progression remains ( Mak et al., 2016 ). In comparison to type I collagen, type V collagen is expressed in relatively low levels in healthy tissues. In cancer, type V collagen, especially the α2 chain, has been shown to be upregulated in colorectal, gastric and breast cancer and is associated with PDAC cell proliferation, invasion, metastasis, and angiogenesis ( Barsky et al., 1982 ; Imamura et al., 1995 ; Sun et al., 2011 ; Berchtold et al., 2015 ; Mak et al., 2016 ; Huang et al., 2017 ; Ren et al., 2018 ; Tan and Chen, 2018 ; Balancin et al., 2020 ; Wang et al., 2021a ; Tan et al., 2021 ). Altogether, this indicates, that type V collagen may be a key factor in determining fibrillar density and hence tumor fibrosis.

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FIGURE 1 . Type V collagen regulates type I collagen architecture. Collagen fibers consist of collagen fibrils, which are made up by self-assembled collagen microfibrils (A) . Type V collagen is incorporated into the type I collagen microfibril structure, where it during homeostasis regulates structural integrity of type I collagen (B) . Type V collagen (low COLV) deficiency results in abnormal type I collagen fibrils and the well-known Ehlers-Danlos syndrome (B) . Augmented type V collagen expression (high COLV) results in more condensed and linearized type I collagen fibrils and dense fibers characteristic of tumor fibrosis (B) . COLI, type I collagen; COLV, type V collagen.

The present study explored the biomarker potential of measuring the C-propeptide of the α2 chain of type V collagen (PRO-C5) in serum from a discovery cohort and a validation cohort of patients with PDAC as well as in 10 non-pancreatic solid tumor types to explore if the PRO-C5 biomarker had relevance in PDAC and other tumor types.

2 Materials and methods

2.1 patients.

The PDAC discovery cohort (Cohort 1), consisted of 19 age- and sex-matched healthy controls, 12 patients with chronic pancreatitis and 33 patients with PDAC (stage I-IV). The PDAC validation cohort (Cohort 2), consisted of 800 patients with PDAC (stage I-IV). Serum samples from patients with chronic pancreatitis and PDAC in cohort 1 and 2 were from the Danish BIOPAC study “Biomarkers in patients with pancreatic cancer (BIOPAC) – can they provide new information of the disease and improve diagnosis and prognosis of the patients” ( ClinicalTrials.gov ID: NCT03311776). The study has been described elsewhere ( Chen et al., 2019 ; Bagni et al., 2020 ; Nissen et al., 2021a ; Nissen et al., 2022 ). The study was carried out in accordance with the Danish Regional Committee on Health Research Ethics. The BIOPAC protocol was approved by the Danish Regional Committee on Health Research Ethics (VEK ref. KA-20060113; and the retrospective protocol VEK H-17039022) and the Data Protection Agency (j.nr. 2006-41-6848, 2012-58-0004, HGH-2015-027; I-Suite j. nr. 03960; and PACTIUS P-2020-834). All subjects gave written informed consent in accordance with the Declaration of Helsinki, version 8. Serum samples were collected before operation or before start of palliative chemotherapy. Clinical data were collected prospectively. The patients were followed until September 2022 or death, whichever came first. Serum samples were measured blinded without information of the clinical characteristics. Clinical data included age, sex, stage (American Joint Commission on Cancer, eighth edition), number of metastatic sites, liver metastasis, body mass index (BMI), diabetes, tobacco use, alcohol use, carbohydrate antigen 19-9 (CA19-9), performance status (PS), Charlson age comorbidity index (CACI) and overall survival (OS). Cohort 3 consisted of 33 age and sex matched healthy controls and 200 patients with different types of non-pancreatic cancers: bladder (n = 20), breast (n = 20), colorectal (n = 20), head and neck (n = 20), kidney (n = 20), lung (n = 20), malignant melanoma (n = 20), ovarian (n = 20), prostate (n = 20), and stomach (n = 20). Serum from patients with cancer in cohort 3 were obtained from the commercial vendor Proteogenex (CA, United States). Healthy controls in cohort 1 and 3 were obtained from Valley BioMedical (VA, United States) and BioIVT (Westbury, NY, United States), respectively. Appropriate Institutional Review Board/Independent Ethical Committee approved sample collection and all subjects filed for informed consent. Patient demographics for cohort 1, 2 and 3 are shown in Tables 1 , 2 , respectively.

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TABLE 1 . Patient demographics for Cohort 1 and Cohort 2.

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TABLE 2 . Patient demographics for Cohort 3.

2.2 Assessment of the C-propeptide of type V collagen fragments (PRO-C5) in human serum

Serum levels of the C-propeptide of type V collagen were measured using the ELISA based assay PRO-C5 according to manufacturer´s instruction (Nordic Bioscience A/S, Denmark). The technical details of the assays have previously been described ( Vassiliadis et al., 2011 ; Vassiliadis et al., 2012 ).

2.3 Statistics

Biomarker results were reported in accordance with the REMARK (reporting recommendations for tumor marker prognostic study) guidelines ( Altman et al., 2012 ). A Kruskal–Wallis multiple comparison test was used to test the difference between PRO-C5 serum levels in healthy controls, and patients with either chronic pancreatitis or PDAC (cohort 1) as well as for PRO-C5 serum levels in healthy controls and in 10 different cancer indications (cohort 3). Non-parametric Mann Whitney tests were used to assess associations with PRO-C5 serum levels in early (stage I-II) and late (stage III-IV) stages of PDAC in cohort 1 and cohort 2. Kaplan-Meier curves were used to assess the association between high and low serum levels of PRO-C5 and OS. To provide granularity on the association between PRO-C5 and overall survival, and to explore a potential cut off proximity to be tested in the validation cohort, the patients in the discovery cohort, cohort 1, were stratified into four groups based on quartiles (Q1, Q2, Q3 and Q4). In cohort 2, patients were stratified based on the 75th percentile, meaning Q1-Q3 vs. Q4 (cut-off: 832 ng/ml). When exploring the association between PRO-C5 serum levels and OS in specific stages of PDAC, patients were stratified based on the 75th percentile, meaning Q1-Q3 vs. Q4 (Stage II cut-off 725 ng/ml; stage III cut-off 792 ng/ml; stage IV cut-off 841 ng/ml). In cohort 1, a univariate Cox proportional-hazard regression model was used to calculate the hazard ratios (HR) with 95% confidence interval (Cl) for short OS per PRO-C5 biomarker levels (Q4, or Q3 or Q2 vs. Q1). In cohort 2, a univariate Cox proportional-hazard regression model was used to calculate the hazard ratios (HR) with 95% confidence interval (Cl) for short OS per PRO-C5 biomarker levels (continuous and Q1-Q3 vs. Q4) and clinical covariates: age (continuous), gender (female vs. male), number of metastatic sites (≥1 vs. 0), liver metastasis (yes vs. no), BMI (continuous), stage (I-II vs. III-IV), diabetes (yes vs. no), tobacco use (ever vs. never), alcohol use (below and above the Danish Health Authority recommendations [DHAR]), CA19-9 (>median vs. ≤ median [median = 483 U/mL]), PS (1 + 2 + 3 vs. 0) and CACI (≥4 vs. < 4). In addition, in cohort 2, a multivariate Cox proportional-hazard regression models including PRO-C5 (continuous and Q1-Q3 vs. Q4), age, metastatic sites (≥1 vs. 0), liver metastasis (yes vs. no), stage (I-II vs. III-IV), CA19-9 (>median vs. ≤ median [median = 483 U/mL]), PS (1 + 2 + 3 vs. 0) and CACI (≥4 vs. < 4) was used to evaluate potential independent prognostic value of the PRO-C5 biomarker for predicting OS. When the model was used for patients in individual stages only age, CA19-9 (>median vs. ≤ median [median = 483 U/mL]), PS (1 + 2 + 3 vs. 0) and CACI (≥4 vs. < 4) were included for stage II and III. For stage IV, age, CA19-9 (>median vs. ≤ median [median = 483 U/mL]), PS (1 + 2 + 3 vs. 0), CACI (≥4 vs. < 4), number of metastatic sites (≥1 vs. 0) and liver metastasis (yes vs. no) were included. Patients in disease stage I were not analyzed due to the low number of patients in this group (n = 15). A p -value of p < 0.05 was considered statistically significant. Graph design and statistical analyses were performed using GraphPad Prism Version 9 (GraphPad Software, Inc.) and MedCalc version 19.3 (Medcalc Software).

3.1 PRO-C5 is elevated in patients with PDAC and associates with poor OS–Discovery cohort

In the discovery cohort, cohort 1, PRO-C5 was significantly elevated in serum from patients with PDAC compared to healthy controls (median PRO-C5 values: PDAC 1071 ng/ml vs. healthy controls 550 ng/ml, p < 0.001). PRO-C5 was not significantly increased in patients with chronic pancreatitis (median PRO-C5 value 786 ng/ml) compared to healthy controls nor in patients with PDAC compared to chronic pancreatitis ( Figure 2A ). When stratifying patients with PDAC into early and late stage (stage I-II vs. III-IV), patients in late stage PDAC had significantly increased PRO-C5 (median PRO-C5 values: 635 ng/ml vs. 1360 ng/ml, respectively, p = 0.0018) ( Figure 2B ).

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FIGURE 2 . PRO-C5 is elevated in serum from patients with pancreatic ductal adenocarcinoma (PDAC) in the discovery cohort. (A) Individual serum PRO-C5 levels in patients with PDAC (n = 33), chronic pancreatitis (n = 12) and healthy controls (19). Differences in PRO-C5 levels between disease indication were analyzed with a Kruskal–Wallis multiple comparison test non-parametric test. (B) Individual serum PRO-C5 levels in patients with early (stage I-II) and late (stage III-IV) stage PDAC. Differences in PRO-C5 levels between early and late stage PDAC were analyzed with a non-parametric Mann Whitney test. Ns, p > 0.05; ** p < 0.01; *** p < 0.001.

To investigate the association between PRO-C5 serum levels and OS, we assessed the prognostic potential of PRO-C5 by Kaplan-Meier curves and a univariate Cox proportional-hazard model. Patients were stratified into quartiles i.e., Q1 containing patient with the lowest levels of PRO-C5 and Q4 containing patients with the highest levels of PRO-C5. Patients in Q1, Q2, Q3 and Q4 had median OS of 28.0 months, 7.1 months, 15.5 months, and 3.8 months, respectively (log-rank, p = 0.0005). Thus, the difference in median OS between Q4 and Q1 were more than 2 years (24.2 months) ( Figure 3 ). In support, univariate Cox proportional-hazard model showed that patients in Q4 had a 940% increased risk of mortality compared with patients in Q1 (Q4 vs. Q1: HR = 10.4, 95% CI 2.9-37.2, p = 0.0003) ( Figure 3 ). There was no significant difference in risk of mortality and PRO-C5 levels between Q4 vs. Q2 and Q4 vs. Q3 ( Figure 3 ).

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FIGURE 3 . High levels of serum PRO-C5 were associated with short overall survival in the discovery cohort. The Kaplan-Meier survival plot shows the association between overall survival and serum PRO-C5. Patients were stratified into quartiles (Q1 (blue) patient with the lowest PRO-C5; and Q4 (orange) patients with the highest levels of PRO-C5). Hazard ratios (HR), 95% confidence intervals (CI) and log-rank test are shown.

3.2 PRO-C5 is elevated in patients with PDAC and associates with poor OS–Validation cohort

In the validation cohort, cohort 2, we were overall able to confirm the findings from the discovery cohort including a PRO-C5 increase in late stage PDAC compared to early stage PDAC ( p = 0.004) ( Figure 4A ). To evaluate the association between PRO-C5 serum levels and OS in the PDAC validation cohort, patients were stratified into two groups based on the quartiles similar to the approach used in cohort 1 above: one containing patients with low levels of serum PRO-C5 (below the Q4 percentile), and another containing patients with high levels of serum PRO-C5 (above the Q4 percentile). Patients with low and high PRO-C5 had a median OS of 10.1 and 6.4 months, respectively (log-rank p < 0.0001) ( Figure 4B ). In addition, univariate Cox proportional-hazard modelling showed that patients with high levels of PRO-C5 had a 50% higher risk of mortality as compared to patients with low levels of PRO-C5 (High PRO-C5 vs. low PRO-C5: HR = 1.5, 95% CI 1.3-1.8, p < 0.0001) ( Figure 4B and Table 3 ). To evaluate if the association of OS and PRO-C5 was independent of clinical covariates, a multivariate Cox proportional-hazard model including age, number of metastatic sites, liver metastasis, stage, CA19-9, PS and CACI was performed. The model showed that the prognostic value of PRO-C5 remained statistically significant when adjusting for these clinical covariates (HR = 1.4, 95% CI 1.2-1.7, p = 0.0001) ( Table 3 ), which indicated that PRO-C5 is a risk factor independent of other common risk factors.

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FIGURE 4 . High levels of serum PRO-C5 were associated with short overall survival in the validation cohort. (A) Individual serum PRO-C5 levels in patients with early (stage I-II) and late (stage III-IV) PDAC. Differences in PRO-C5 levels between early and late stage PDAC were analyzed with a non-parametric Mann Whitney test. (B) A Kaplan-Meier survival plot shows the association between overall survival and levels of PRO-C5. Patients were stratified into low (Q1-Q3, blue) and high (Q4, orange) PRO-C5 (cutoff, 832 ng/ml). Hazard ratios (HR), 95% confidence intervals (CI) and log-rank test are shown. *** p < 0.001.

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TABLE 3 . Uni- and multivariate cox regression analysis in 800 patients with pancreatic ductal adenocarcinoma stage I-IV.

Next, we wanted to gain more granularity on the association between high serum PRO-C5 and OS in patients stratified into specific stages of PDAC. Patients in disease stage I were not analyzed due to the low number of patients in this group (n = 15). For each cancer stage, patients were stratified into high and low PRO-C5 using the 75th percentile as a cutoff.

Patients with stage II disease (n = 117) and low levels of PRO-C5 had a medium OS at 24.3 months compared to 8.5 months in patients with low PRO-C5 (log rank test, p = 0.0041) ( Figure 5A ). Thus, the difference in median OS between the two groups was more than 1 year (15.8 months). Univariate Cox proportional-hazard model showed that patients with stage II PDAC and high levels of PRO-C5 had a 100% increased risk of death compared to patients with low PRO-C5 (HR = 2.0, 95% CI 1.2-3.3, p = 0.0049) ( Figure 5A ). A multivariate Cox proportional-hazard model including age, CA19-9, PS and CACI showed that the association between high PRO-C5 and short OS was independent of the clinical variables in patients with stage II disease (HR = 2.0, 95% CI 1.2-3.4, p = 0.010) ( Table 4 ).

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FIGURE 5 . High levels of serum PRO-C5 were associated with short overall survival in patients with PDAC according to stage II, III and IV in the validation cohort. Kaplan-Meier survival plots show the association between overall survival and levels of PRO-C5 in stage II (A) , stage III (B) and stage IV patients (C) . In all plots, patients were stratified into low (Q1-Q3, blue) and high (Q4, orange) PRO-C5 (Stage II: cut-off 725 ng/ml, stage III: cut-off 792 ng/ml, stage IV: cut-off 841 ng/ml). Hazard ratios (HR), 95% confidence intervals (CI) and log-rank test are shown.

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TABLE 4 . Multivariate Cox proportional-hazard regression model in patients with pancreatic ductal adenocarcinoma divided into stage II, III and IV.

Patients with stage III disease (n = 227) and low levels of PRO-C5 had a median OS of 13.1 months compared to 9.5 months in patients with high PRO-C5 (log rank test, p = 0.0191) ( Figure 5B ). Univariate Cox proportional-hazard model showed that patients with stage III disease and high PRO-C5 had a 50% increased risk of death compared to patients with low PRO-C5 (HR = 1.5, 95% CI 1.1-2.1, p = 0.0191) ( Figure 5B ). A multivariate Cox proportional-hazard model including age, CA19-9, PS and CACI showed that the association between high PRO-C5 and short OS was independent of the clinical variables in patients with stage III disease (HR = 1.5, 95% 1.1-2.1, p = 0.0177) ( Table 4 ).

Patients with stage IV disease (n = 435) and low levels of PRO-C5 had a median OS of 6.3 months compared to 4.8 months in patients with high PRO-C5 (log rank test, p = 0.0012) ( Figure 5C ). Univariate Cox proportional-hazard model showed that patients with stage IV disease and high PRO-C5 had a 40% increased risk of death compared to patients with low PRO-C5 (HR = 1.4, 95% CI 1.1-1.7, p = 0.0012) ( Figure 5C ). A multivariate Cox proportional-hazard model including age, CA19-9, PS, CACI, number of metastatic sites and liver metastasis showed that the association between high PRO-C5 and short OS was independent of the clinical variables in patients with stage IV disease (HR = 1.3, 95% CI 1.1-1.6, p = 0.0085) ( Table 4 ).

3.3 PRO-C5 is increased in serum from patients with different non-pancreatic types of cancer

Next, we wanted to explore the PRO-C5 biomarker potential in other non-pancreatic cancer types (cohort 3). Bladder-, breast-, colorectal-, head and neck-, kidney-, lung-, ovarian cancer and melanoma had significantly elevated PRO-C5 levels compared to healthy controls ( p < 0.05 to 0.0001), whereas this was not found for patients with prostate- and stomach cancer Figure 6 . PRO-C5 levels for individual stages in each cancer disease can be seen in S1.

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FIGURE 6 . PRO-C5 was elevated in serum from patients with different types of cancer. PRO-C5 individual measurements in patients with different non-pancreatic types of cancer: bladder cancer (n = 20), breast cancer (n = 20), colorectal cancer (n = 20), head and neck cancer (n = 20), kidney cancer (n = 20), lung cancer (n = 20), malignant melanoma (n = 20), ovarian cancer (n = 20), prostate cancer (n = 20) or stomach cancer (n = 20); and compared to healthy controls (n = 33). Bar plots showing the median PRO-C5 value. A Kruskall-Wallis test was used to analyze the difference in PRO-C5 between cancer types. Ns, non-significant; * p < 0.05; *** p < 0.001; **** p < 0.0001.

4 Discussion

In this study we evaluated the biomarker potential of measuring the α2 chain of the type V collagen C-propeptide (PRO-C5) in serum from patients with cancer. In a discovery cohort we found that serum PRO-C5 was increased in patients with PDAC compared to healthy controls. Furthermore, high levels of PRO-C5 were associated with locally advanced or metastatic PDAC and patients with PDAC with high serum PRO-C5 had increased risk of dying compared to patients with low levels. The results were validated in a large group of 800 patients with PDAC where high PRO-C5 was associated with poor OS in stage II, III and IV independent of other risk factors including PS and CA19-9. Interestingly, the largest relative difference in OS was seen for patients in stage II where the median OS was more than 1 year longer in patients with low PRO-C5 compared to patients with high PRO-C5. In comparison, CA19-9 was also independently associated with OS in patients with stage III and IV disease, but not for patients in stage II. We also showed a relevance of PRO-C5 in other solid tumor types as supported by the gene-expression of the α2 chain that has been shown to be upregulated in many different types of cancer indications ( Barsky et al., 1982 ; Imamura et al., 1995 ; Sun et al., 2011 ; Berchtold et al., 2015 ; Mak et al., 2016 ; Huang et al., 2017 ; Ren et al., 2018 ; Tan and Chen, 2018 ; Balancin et al., 2020 ; Wang et al., 2021a ; Tan et al., 2021 ).

Similar to PRO-C5, other biomarkers originating from the tumor fibrotic compartment have shown potential as prognostic and predictive biomarkers in various types of cancers including PDAC ( SN et al., 2018 ; Willumsen et al., 2018 ; Jensen et al., 2020a ; Jensen et al., 2020b ; Nissen et al., 2021a ; Nissen et al., 2021b ; Wang et al., 2021b ; Jensen et al., 2021 ; Nissen et al., 2022 ; Willumsen et al., 2022 ). PRO-C3, measuring the formation of type III collagen, has been reported to be prognostic for OS in patients with PDAC ( Willumsen et al., 2019 ; Chen et al., 2020 ; Nissen et al., 2022 ). Moreover, the turnover of type III collagen is predictive of response to PEGPH20, an experimental anti-fibrotic drug ( Wang et al., 2021b ). Like type I collagen, type III collagen is a major fibrillar collagen present in both healthy and diseased tissue ( Ricard-Blum, 2011 ). In contrast to type I and type III collagen which make up the bulk of a fiber, type V collagen is regarded as a minor collagen assisting the major fibrillar collagens in the assembly of a fiber. Lately, other minor collagens, such as the fibrillar type XI and the FACIT collagens (type XIX, XX and XXII) have gained interest as more disease specific biomarkers and/or targets. Similar to what we show for type V collagen here, our group have earlier shown that biomarkers that measure type XI, XIX, XX and XXII collagens are also upregulated in different types of cancers ( Thorlacius-Ussing et al., 2020 ; Nissen et al., 2021a ; Madsen et al., 2022 ; Thorlacius-Ussing et al., 2022 ). In addition, high serum levels of type XI, XX and XXII collagens were all prognostic for short OS in patients with PDAC ( Nissen et al., 2021a ; Madsen et al., 2022 ; Thorlacius-Ussing et al., 2022 ). These minor collagens are mainly expressed in high levels during embryogenesis and in cancer progression, compared to the relative upregulation of major collagens, which are already present in high amount. Despite the fact that the major type I collagen is important for tumor progression and interacts closely with type V collagen, a biomarker measuring serum type I collagen formation was not increased in the same cohort of different tumor types compared to controls as measured here for PRO-C5 (cohort 3) ( Madsen et al., 2022 ). This supports, that alterations in tumor fibrosis goes beyond type I collagen. Part of this explanation may be that type I collagen is the most abundant protein in the body, and therefore may have less sensitivity as a serological biomarker than the less abundant minor type V collagen, which also underlines the important role of type V collagen in tumor fibrosis. PRO-C5 may have the potential to be used as a treatment guide already in stage II PDAC, and to monitor drug efficacy and detect responders to different treatments. Interestingly, the present study suggests that PRO-C5 may be applicable in many other solid cancer types.

Tumor fibrosis results in stiff tissue, and we and others have earlier shown that CAFs produce more linearized and aligned collagen fibers ( Drifka et al., 2015 ; Drifka et al., 2016a ; Bolm et al., 2020 ; Nissen et al., 2022 ). Cancer cells are believed to use these linearized collagen fibers to metastasize ( Drifka et al., 2016b ). When the type V collagen/type I collagen ratio increases, the fibrils become smaller in vitro ( Adachi and Hayashi, 1986 ; Birk et al., 1990 ). What this exactly means for biological function is still unknown. Recently, Chen et al., showed that pancreatic cancer cells produce unique type I collagen homotrimers (α1/α1/α1) in comparison to the type I collagen heterotrimers (α1/α2/α1) produced by fibroblasts ( Chen et al., 2022 ). Moreover, they showed that deletion of type I collagen homotrimers increased survival in a PDAC mouse model and increased T-cell infiltration and efficacy toward anti-PD-1 immunotherapy ( Chen et al., 2022 ). Studies have also shown that type V collagen can exist in both homo- and heterotrimers, e.g., as α1(V) 2 α2(V), α1(V) 3 or α1(V)α2(V)α3(V) ( Chanut-Delalande et al., 2001 ; Chanut-Delalande et al., 2004 ; Mak et al., 2016 ), but the impact of this is yet to be determined. It could be discussed if the homotrimer structure of type I collagen could actually be affected by type V collagen. In line with this, Chen et al., showed that pancreatic cancer cells expressing Col1α1, but not Col1α2, had an elevation of Col5α2 expression ( Chen et al., 2022 ). Altogether these data could lead to the hypothesis, that increased type V collagen expression leads to more linearized type I collagen fibers promoting tumor progression and metastasis.

Some confounders in this study should be mentioned. Selection bias in the BIOPAC cohort may occur, as only patients in good performance for operation or palliative chemotherapy were included. Moreover, several publications have shown that PRO-C5 is associated with liver fibrosis, and it could be speculated if the high PRO-C5 levels are an indirect measure of liver metastases ( Vassiliadis et al., 2011 ; Vassiliadis et al., 2012 ; Leeming et al., 2015 ). However, we found that the prognostic value of PRO-C5 was independent of liver metastases which support that the measured PRO-C5 originates from the tumor fibrosis compartment.

In conclusion, the C-propeptide of the minor fibrillar type V collagen is elevated in serum from patients with cancer. In addition, high levels are independently associated with short OS in patients with PDAC, especially patients with stage II disease. This emphasizes the importance and complexity of tumor fibrosis. PRO-C5 may have the potential of guidance in many aspects within drug discovery, patient stratification and drug efficacy.

Data availability statement

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Ethics statement

The studies involving human participants were reviewed and approved by Danish Regional Committee on Health Research Ethics. The patients/participants provided their written informed consent to participate in this study.

Author contributions

Conception of the work: all authors. Drafting of the article: NN and NW. Biomarker measurements: NN. Preparing figures: NN. Patient inclusion and sample collection: AJ, IC, CH, JJ, HD, and LJ. Collection of clinical data: AJ, IC, CH, and JJ. Critical revision of the article: All authors. Final approval: all authors.

Conflict of interest

NN, CJ, EM, JT-U, MK, and NW are all employed by Nordic Bioscience A/S.

The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

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Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmolb.2023.1158058/full#supplementary-material

Supplementary Figure S1 | PRO-C5 levels in independent stages of varies cancer diseases. I: stage I, II: stage II, III: stage III, IV: stage IV.

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Keywords: cancer, collagen, PDAC, prediction, prognosis, tumor fibrosis, type V collagen

Citation: Nissen NI, Johansen AZ, Chen IM, Jensen C, Madsen EA, Hansen CP, Thorlacius-Ussing J, Karsdal M, Johansen JS, Diab HMH, Jørgensen LN and Willumsen N (2023) High serum levels of the C-propetide of type V collagen (PRO-C5) are prognostic for short overall survival in patients with pancreatic ductal adenocarcinoma. Front. Mol. Biosci. 10:1158058. doi: 10.3389/fmolb.2023.1158058

Received: 03 February 2023; Accepted: 23 February 2023; Published: 10 March 2023.

Reviewed by:

Copyright © 2023 Nissen, Johansen, Chen, Jensen, Madsen, Hansen, Thorlacius-Ussing, Karsdal, Johansen, Diab, Jørgensen and Willumsen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Neel I. Nissen, [email protected]

This article is part of the Research Topic

The Role of The Extracellular Matrix in Tumor Progression and Therapeutic Resistance - Volume II

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‘Scream VI’ Review: Ghostface Takes Manhattan as This Slasher Franchise Finds Its Footing Again

Matt bettinelli-olpin and tyler gillett's second "scream" movie is a massive improvement — and proof that there's life after wes craven for this slasher franchise..

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Christian Zilko

Mar 8, 2023 3:04 am

"Scream VI"

“Scream VI”

©Paramount/Courtesy Everett Collection

If there’s one thing we’re supposed to take away from “ Scream VI ,” it’s that this meta horror series is officially a franchise now. Of course, the idea that it wasn’t already would certainly be news to Paramount executives. Any series that lasts long enough to spawn six movies is a franchise in the literal sense of the word. But up to this point, the Wes Craven-created property had gone to great lengths to differentiate itself from the slasher franchises it loves to lampoon.

“Friday the 13th” and “Nightmare on Elm Street” and all of their ilk are the poster children for quantity-based filmmaking. They exist in worlds where continuity is nonexistent, supporting characters come and go without ever being missed, and the bad guy can never be definitively killed. There’s never been a serious attempt to wrap up the overarching narrative — and you know there’s never going to be — because the franchise is bigger than any one actor or director. Those movies are going to keep coming out until the heat death of the universe, and loyal fans will keep seeing them out of sunk costs and the possibility that a bold filmmaker can turn a cheaply made sequel into a diamond in the rough (looking at you, “Jason X”).

There’s no denying that the “Scream” movies come awfully close to matching that description, but they’ve always been able to toe the line without crossing it. Up to now, each sequel has used a self-referential framing device to justify its own existence: “Scream 2” mocked horror sequels, “Scream 3” explored the way trilogy endings differ from their predecessors, “Scream 4” poked fun at the prevalence of remakes, and last year’s “Scream” made a convoluted attempt to comment on “elevated horror” and reboots that bring back legacy characters.

Those narrative devices offered a shred of plausible deniability against charges that the “Scream” series was just an endless assembly line of slasher whodunnits. Anyone who felt like using semantics to defend the series could plausibly make the claim that changes to the horror movie ecosystem necessitated each of the four sequels.

No more. While “Scream VI” still features its share of meta humor, it leaves no doubt that this universe is now fleshed out enough to support an infinite number of sequels that aren’t parodies of industry trends. And the film’s ability to shine without the involvement of Craven (who died in 2015) is a clear sign that the “Scream” series can afford to lose any of its key players if it’s smart about replacing them.

L-r, Dermot Mulroney (“Detective Bailey “), Jenna Ortega (“Tara Carpenter”), Jack Champion (“Ethan Landry“), Hayden Panettiere (“Kirby Reed”), Jasmin Savoy Brown (“Mindy Meeks-Martin”), Melissa Barrera (“Sam Carpenter”) and Mason Gooding (“Chad Meeks-Martin”) star in Paramount Pictures and Spyglass Media Group's "Scream VI."

Philippe Bossé

Matt Bettinelli-Olpin and Tyler Gillett’s tenure at the helm of the franchise got off to a rocky start when their 2022 reboot clearly lacked Craven’s wit and visual panache. But their second “Scream” film sees them stepping out of Craven’s shadow entirely, proving that there’s plenty of room for new filmmakers to put their own spin on the series.

The last “Scream” movie was an obvious reset for the franchise. The self-described “re-quel” brought back fan favorites like Courteney Cox and David Arquette, but it primarily focused on introducing a new generation of stars to fight Ghostface. That film saw two horror junkies attempting to film their own remake of the fictional “Stab” movies by initiating a new set of murders in Woodsboro. While the killers were eventually caught, survivors like Sam (Melissa Barrera) and Tara (Jenna Ortega) Carpenter and Chad (Mason Gooding) and Mindy (Jasmin Savoy Brown) Meeks-Martin were traumatized for life.

“Scream VI” picks up right where that left off, following the two sets of siblings to New York City after they made the all-too-rational decision to leave town after the killing spree. Now they’re trying to adapt to life as college freshmen, but it quickly becomes clear that they can’t just run from their Ghostface problem. Sam has become the subject of a brutal online harassment campaign because a conspiracy theory claimed that she was the actual killer in Woodsboro. And Tara is trying to break free of her overprotective sister, who won’t let her out of her sight. When a film studies professor gets stabbed to death by a guy in a Ghostface mask, they know it’s only a matter of time before the latest movie-obsessed killer comes for them. Their only recourse is to find him first.

Of course, it wouldn’t be a “Scream” movie without characters using their knowledge of real horror movies to protect themselves. As they begin to narrow down the list of suspects, it dawns on them that they’re living in a full-fledged franchise now. That means that many of the old “rules” that characters have used to survive previous installments are useless. Everyone is on edge once they realize that anyone can die at any moment — romantic leads and fan favorite characters aren’t safe anymore. The only thing left to do is brace themselves for a bigger, bloodier face-off with their new assailant.

“Scream VI” is a clear continuation of what Bettinelli-Olpin and Gillett established in “Scream,” but it improves on the “re-quel” in just about every way. The college setting allows the young leads to take center stage, freeing up the legacy characters to add color at all the right moments without having to carry the film. (If it wasn’t obvious already, it’s time to acknowledge that Cox’s Gale Weathers is one of the best human characters that the horror genre has ever produced. The idea of a grifty investigative journalist who will do anything to monetize her proximity to tragedies becomes more plausible with each passing film, and Cox flawlessly alternates between genuine competence and sleazy opportunism.)

L-r, Mason Gooding (“Chad Meeks-Martin”), Jenna Ortega (“Tara Carpenter”), Jasmin Savoy Brown (“Mindy Meeks-Martin”), Devyn Nekoda (“Anika Kayoko”) and Melissa Barrera (“Sam Carpenter”) star in Paramount Pictures and Spyglass Media Group's "Scream VI."

And more than anything, it’s just really fucking fun . The set pieces are bigger, the killer reveal is twistier, and the film actually uses its New York setting to its full advantage. (Unlike the abysmal “Jason Takes Manhattan,” which devotes the majority of its runtime to the boat ride that took Jason Voorhees to Manhattan and treats his actual time in the city like an epilogue.) While the camerawork sometimes falls short of the formalism that Craven spent a lifetime honing, this film zips along with the energy of something that was clearly made in the 2020s. The whole movie is living proof that the franchise has plenty of gas left in the tank —and that we should all be excited about the inevitable “Scream VII.”

Without spoiling anything about who survives the latest film, it goes without saying that almost everyone will outgrow this franchise eventually. Characters will be killed off, actors will distance themselves from the slasher world in search of bigger roles, and directors like Bettinelli-Olpin and Gillett will eventually move onto other projects. But if there’s one thing that the “Scream” franchise has taught us, it’s that there’s always someone new waiting to put on the mask. If they keep making ’em like “Scream VI,” the future is as bright as it is bloody.

Paramount will release “Scream VI” in theaters on Friday, March 10.

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This Article is related to: Film , Reviews and tagged Reviews , Scream 6 , Scream VI

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'School Spirits' Review: Peyton List Leads a Supernatural Show Full of Mystery and Heart

High school has never been so haunting.

There’s that amusing little notion that high school is supposed to be “the best years of your life.” But what if those years walking those hallways went on for all eternity? Created by Megan and Nate Trinrud , and based on their forthcoming graphic novel, Paramount+’s new YA mystery series School Spirits follows Maddie Nears, played by Cobra Kai star Peyton List , who is stuck in the afterlife after being murdered in her high school's boiler room. The kicker: high school is the afterlife. Whenever someone dies on school grounds, they lurk around in purgatory at Split River High, unable to step foot beyond campus. Out of all the imagined concepts of Hell in television and film, an eternity of high school might just be the most punishing.

Maddie is joined by a group of eccentric teenage ghosts from previous decades who are also trapped in limbo at Split River High: Charley ( Nick Pugliese ), a gay student from the '90s who takes Maddie under his wing and shows her the ropes in the afterlife, Wally ( Milo Manheim ), a lovable ‘80s jock, and Rhonda ( Sarah Yarkin ), a disillusioned beatnik with a penchant for lollipops and Jack Kerouac. Unlike her fellow “school spirits,” Maddie doesn’t remember how she died, aside from the fact that her blood was found in the boiler room of the school. She dives headfirst into an investigation, desperate to find out what exactly happened in her final moments on Earth that led to her tragic demise. In the land of the living, she is considered a “missing person,” with her body having not been found. Her best friends, Simon ( Kristian Flores ) and Nicole ( Kiara Pichardo ) — alive and very much not well — also start their own investigation in the hopes that Maddie is still alive.

RELATED: 'School Spirits': Release Date, Cast, Filming Details, and Everything We Know so Far About the Supernatural Series

As a young adult drama — and a supernatural one at that — School Spirits could have easily been a drop in the bucket in a genre that is already filled to the brim with forgettable, lukewarm stories. But School Spirits holds its own as a surprisingly refreshing take on the YA murder mystery genre, and that’s largely due to its commitment to character work. Although the mystery of who killed Maddie is intriguing enough, School Spirits doesn’t rely on it to keep its viewers watching. Consider popular YA thrillers that quickly spun off the rails, like Pretty Little Liars or Riverdale , due to increasingly ludicrous “twists” as a ploy to maintain viewership. (Although interestingly, Oliver Goldstick of Pretty Little Liars is the showrunner/producer on School Spirits .) The mystery behind Maddie’s murder is a perfect hook, but it’s the characters themselves and the performances of its young actors that will bring viewers back.

The gang of misfits in the afterlife have that colorful flair of characters who practically leap from the pages of a graphic novel to the small screen. In the same vein as successful graphic novel adaptations like The Umbrella Academy , the ensemble is composed of larger-than-life characters who could be pigeonholed into a stereotype without the right touch. The characters could be one-dimensional, a prototype of their respective decades, but School Spirits takes time to give each one a voice to tell their story. Although this review only covers the first three episodes, there are of course characters yet to be explored — but with its introduction, the series is laying a strong foundation for its cast.

List and Flores, in particular, deliver impressive performances as two young people grappling with the horror of the unknown. List proves that she can certainly hold her own as a lead rather than a supporting character (although one could argue that the entire ensemble of Cobra Kai are the leads). She captures the panic and resolute determination of a leading girl who will stop at nothing to take back the story that was violently snatched from her. Flores’ performance as Simon is so genuine that in one particular scene, his vulnerability and grief over losing a best friend is so real that it breaks your heart. Like with many YA murder mysteries, some of the plot twists and big reveals are somewhat predictable, but it’s not necessarily to the show’s detriment. With there being five episodes left, there will surely be plenty of time for more twists and turns. Each of the first three episodes provided for review manages to deliver at least one satisfying surprise.

A major reason why School Spirits ' mystery works, even despite some predictability, is because of its unique twist on the genre. The idea of living an afterlife in the very same high school you attended — let’s be honest, any high school — is a hell one wouldn’t wish on their worst enemy. This setting adds an extra layer of drama as Maddie watches her classmates quickly move on from her disappearance without a care in the world. The other members of the afterlife crew also have the painful experience of watching time go on for decades of change without them. Even if some twists are predictable, the emotional journey the characters are going through — whether they are among the living and suffering a loss of a friend with no answers, or among the dead and robbed of a full life — this type of character work makes up for a little predictability.

There are also a few subtle touches sprinkled throughout the first three episodes that evoke that bite of teen angst but ultimately sincere tone that School Spirits is aiming for. The soundtrack ( Phoebe Bridgers ’ “I know The End” is a perfect match for the conclusion of the first episode) and the '90s grunge style that Maddie rocks captures the show's balance of teen thriller and a genuine drama. With School Spirits , the Trinrud siblings ask you what you would do if your story is taken from you, if you had to watch from the outside as life moves on without you. For a YA series, it pulls off these types of emotional themes without seeming forced or insincere. School Spirits will reel you in with its overarching mystery, but it will keep you hooked with its heart.

The first three episodes of School Spirits drop on Paramount+ on March 9.

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