Specifies the number of studies evaluated orselected
Steps, and targets of constructing a good review article are listed in Table 3 . To write a good review article the items in Table 3 should be implemented step by step. [ 11 – 13 ]
Steps of a systematic review
Formulation of researchable questions | Select answerable questions |
Disclosure of studies | Databases, and key words |
Evaluation of its quality | Quality criteria during selection of studies |
Synthesis | Methods interpretation, and synthesis of outcomes |
It might be helpful to divide the research question into components. The most prevalently used format for questions related to the treatment is PICO (P - Patient, Problem or Population; I-Intervention; C-appropriate Comparisons, and O-Outcome measures) procedure. For example In female patients (P) with stress urinary incontinence, comparisons (C) between transobturator, and retropubic midurethral tension-free band surgery (I) as for patients’ satisfaction (O).
In a systematic review on a focused question, methods of investigation used should be clearly specified.
Ideally, research methods, investigated databases, and key words should be described in the final report. Different databases are used dependent on the topic analyzed. In most of the clinical topics, Medline should be surveyed. However searching through Embase and CINAHL can be also appropriate.
While determining appropriate terms for surveying, PICO elements of the issue to be sought may guide the process. Since in general we are interested in more than one outcome, P, and I can be key elements. In this case we should think about synonyms of P, and I elements, and combine them with a conjunction AND.
One method which might alleviate the workload of surveying process is “methodological filter” which aims to find the best investigation method for each research question. A good example of this method can be found in PubMed interface of Medline. The Clinical Queries tool offers empirically developed filters for five different inquiries as guidelines for etiology, diagnosis, treatment, prognosis or clinical prediction.
As an indispensable component of the review process is to discriminate good, and bad quality researches from each other, and the outcomes should be based on better qualified researches, as far as possible. To achieve this goal you should know the best possible evidence for each type of question The first component of the quality is its general planning/design of the study. General planning/design of a cohort study, a case series or normal study demonstrates variations.
A hierarchy of evidence for different research questions is presented in Table 4 . However this hierarchy is only a first step. After you find good quality research articles, you won’t need to read all the rest of other articles which saves you tons of time. [ 14 ]
Determination of levels of evidence based on the type of the research question
I | Systematic review of Level II studies | Systematic review of Level II studies | Systematic review of Level II studies | Systematic review of Level II studies |
II | Randomized controlled study | Crross-sectional study in consecutive patients | Initial cohort study | Prospective cohort study |
III | One of the following: Non-randomized experimental study (ie. controlled pre-, and post-test intervention study) Comparative studies with concurrent control groups (observational study) (ie. cohort study, case-control study) | One of the following: Cross-sectional study in non-consecutive case series; diagnostic case-control study | One of the following: Untreated control group patients in a randomized controlled study, integrated cohort study | One of the following: Retrospective cohort study, case-control study (Note: these are most prevalently used types of etiological studies; for other alternatives, and interventional studies see Level III |
IV | Case series | Case series | Case series or cohort studies with patients at different stages of their disease states |
Rarely all researches arrive at the same conclusion. In this case a solution should be found. However it is risky to make a decision based on the votes of absolute majority. Indeed, a well-performed large scale study, and a weakly designed one are weighed on the same scale. Therefore, ideally a meta-analysis should be performed to solve apparent differences. Ideally, first of all, one should be focused on the largest, and higher quality study, then other studies should be compared with this basic study.
In conclusion, during writing process of a review article, the procedures to be achieved can be indicated as follows: 1) Get rid of fixed ideas, and obsessions from your head, and view the subject from a large perspective. 2) Research articles in the literature should be approached with a methodological, and critical attitude and 3) finally data should be explained in an attractive way.
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Article reviews are an essential part of academic article writing , providing an opportunity to evaluate and analyze published research . A well-written review can help readers understand the simple subject matter and determine the value of the article . In this article, we’ll cover what is an article review, provide step-by-step guidance on how to write one, and answer some common questions.
An article review is a critical assessment of a scholarly article or research paper. It involves analyzing the content, methodology, and findings of the article and providing an evaluation of its strengths and weaknesses. The review typically includes a summary of the article’s main points, an evaluation of its contribution to the subject, and suggestions for improvement.
1. literary analysis of “the great gatsby”.
Title : “The American Dream in F. Scott Fitzgerald’s ‘The Great Gatsby'” Summary : This article delves into the theme of the American Dream in “The Great Gatsby”. It explores how the characters of Jay Gatsby, Daisy Buchanan, and Tom Buchanan each represent different facets of this dream. The review highlights the contrast between Gatsby’s idealistic pursuit of wealth and love, and the moral decay of society depicted in the novel. Evaluation : The article offers a thorough and insightful analysis, drawing on specific passages to support its claims. However, it occasionally lacks depth in exploring secondary characters. Recommendation : Overall, this article is a valuable resource for understanding the complexities of the American Dream in Fitzgerald’s work. It is recommended for students and literary enthusiasts.
Title : “Impact of Global Warming on Arctic Ice Melting Rates” Summary : This article examines recent research on the accelerated melting of Arctic ice due to global warming. The study uses satellite data and climate models to project future ice loss and its implications for global sea levels. Evaluation : The article presents data in a clear and accessible manner, making complex scientific concepts understandable for a general audience. The visual aids, such as graphs and maps, effectively complement the text. Recommendation : This article is highly recommended for anyone interested in climate science and environmental studies. It provides a comprehensive overview of current research and its global significance.
Title : “A Comprehensive Review of the iPhone 14 Pro” Summary : The article provides an in-depth review of the iPhone 14 Pro, covering its design, performance, camera capabilities, and new features. It compares the latest model with previous versions and other smartphones on the market. Evaluation : The review is detailed and well-organized, highlighting both strengths and weaknesses of the device. However, it could benefit from more user testimonials to provide a broader perspective. Recommendation : This review is a must-read for potential buyers considering the iPhone 14 Pro. It offers valuable insights into the device’s capabilities and overall performance.
Title : “The Health Benefits of Practicing Yoga Daily” Summary : This article explores the various physical and mental health benefits of incorporating yoga into a daily routine. It discusses how yoga can improve flexibility, reduce stress, and enhance overall well-being. Evaluation : The article is informative and engaging, backed by scientific research and expert opinions. It includes practical tips for beginners and links to additional resources. Recommendation : This article is highly recommended for individuals seeking to improve their health through yoga. It provides a comprehensive guide to the benefits and practice of yoga.
Title : “The Role of Codebreakers in World War II” Summary : The article examines the critical role that codebreakers played in the Allied victory during World War II. It focuses on the efforts at Bletchley Park and the breaking of the Enigma code. Evaluation : The article is well-researched and presents a compelling narrative of the contributions of codebreakers. It includes firsthand accounts and historical documents to support its analysis. Recommendation : This article is recommended for history buffs and students. It offers a fascinating insight into a lesser-known aspect of World War II and highlights the importance of intelligence work in warfare.
Review of “the effects of sleep deprivation on cognitive performance”.
Title : The Effects of Sleep Deprivation on Cognitive Performance: A Detailed Review Introduction : This review evaluates the article’s investigation into how lack of sleep affects cognitive functions such as memory, attention, and problem-solving skills. Summary : The article explores various studies showing that sleep deprivation significantly impairs cognitive performance, leading to reduced attention spans, poor memory retention, and slower reaction times. Critique : The article is thorough in its examination of the negative effects of sleep deprivation. However, it could include more information on the long-term consequences and potential mitigation strategies. Some studies cited have small sample sizes, which could limit the findings’ reliability. Conclusion : Overall, the article effectively highlights the critical impact of sleep on cognitive functions, though it would benefit from more comprehensive data and solutions to counteract sleep deprivation.
Title : Renewable Energy Sources and Their Impact on the Environment: An In-Depth Review Introduction : This review analyzes the article discussing the environmental impacts of various renewable energy sources, including solar, wind, and hydroelectric power. Summary : The article covers the benefits of renewable energy in reducing carbon emissions and dependence on fossil fuels. It also examines potential environmental concerns such as habitat disruption and resource consumption. Critique : The article provides a balanced view of renewable energy’s benefits and challenges. However, it lacks detailed case studies and comparative analysis with non-renewable energy sources. The discussion on environmental impacts could be more nuanced. Conclusion : The article is informative and highlights the importance of renewable energy, though it would be stronger with more specific examples and a deeper environmental impact analysis.
Title : The Influence of Advertising on Consumer Behavior: A Comprehensive Review Introduction : This review evaluates the article’s exploration of how advertising affects consumer purchasing decisions and behavior. Summary : The article examines various advertising techniques and their psychological effects on consumers, including the use of emotional appeal, repetition, and celebrity endorsements. Critique : The article effectively discusses different advertising strategies and their impact on consumers. However, it could include more recent examples and data to reflect current trends. Additionally, it would benefit from a broader range of perspectives, including consumer psychology. Conclusion : The article provides a solid overview of advertising’s influence on consumer behavior, but it needs more up-to-date examples and a wider scope of analysis.
Title : The Role of Nutrition in Child Development: An Analytical Review Introduction : This review analyzes the article’s discussion on the critical role of nutrition in children’s physical and cognitive development. Summary : The article highlights the importance of a balanced diet for children’s growth, emphasizing nutrients such as proteins, vitamins, and minerals. It also examines the consequences of malnutrition and dietary deficiencies. Critique : The article is well-researched and presents a comprehensive view of the subject. However, it could benefit from more practical dietary recommendations and a discussion on the challenges faced by different socioeconomic groups. Conclusion : The article effectively underscores the importance of nutrition in child development, though it would be improved by including practical advice and addressing socioeconomic disparities.
Title : Artificial Intelligence in Healthcare: Opportunities and Challenges: A Detailed Review Introduction : This review evaluates the article’s exploration of the potential benefits and obstacles of implementing artificial intelligence (AI) in healthcare. Summary : The article discusses various AI applications in healthcare, such as diagnostic tools, personalized medicine, and administrative support. It also addresses ethical concerns, data privacy issues, and the need for regulatory frameworks. Critique : The article provides a balanced and insightful analysis of AI in healthcare. However, it could include more case studies and examples of successful AI implementations. The discussion on ethical concerns is somewhat limited and could be expanded. Conclusion : The article offers a thorough overview of AI’s potential in healthcare, but it would benefit from more real-world examples and a deeper exploration of ethical issues.
Review of “the impact of remote work on employee productivity”.
Title : The Impact of Remote Work on Employee Productivity: A Research Review Introduction : This review assesses the research article’s investigation into how remote work influences employee productivity, examining both positive and negative aspects. Summary : The research article explores various factors affecting productivity in remote work settings, such as flexible schedules, work-life balance, and the use of digital communication tools. It presents data from surveys and case studies to support its findings. Critique : The article provides a comprehensive analysis backed by empirical data. However, it could benefit from a more detailed exploration of the long-term impacts of remote work and potential industry-specific variations. Additionally, the research could include a larger, more diverse sample size. Conclusion : The research article effectively highlights the key factors influencing productivity in remote work environments, though it would be strengthened by broader data and long-term impact analysis.
Title : Climate Change and Agricultural Sustainability: A Review of Current Research Introduction : This review evaluates the research article’s examination of the relationship between climate change and agricultural sustainability, focusing on crop yields and farming practices. Summary : The article discusses the effects of changing weather patterns, increased CO2 levels, and extreme weather events on agricultural productivity. It includes case studies and statistical models to illustrate potential future scenarios. Critique : The research is thorough and well-supported by data. However, it could include more practical recommendations for farmers and policymakers. The article would also benefit from a more detailed discussion of regional differences and adaptation strategies. Conclusion : The research article provides valuable insights into the challenges posed by climate change to agriculture, though it would be improved by offering actionable solutions and considering regional variations.
Title : The Role of Artificial Intelligence in Modern Healthcare: A Comprehensive Research Review Introduction : This review analyzes the research article’s exploration of AI’s applications in healthcare, including diagnostic tools, patient care, and administrative efficiency. Summary : The article outlines various AI technologies used in healthcare, such as machine learning algorithms for diagnostics, robotic surgeries, and AI-driven patient management systems. It presents data from clinical trials and expert opinions to support its claims. Critique : The research is well-rounded and provides a clear overview of AI’s potential in healthcare. However, it could address more of the ethical considerations and data privacy issues associated with AI implementation. Additionally, more real-world examples of AI applications would enhance the article’s relevance. Conclusion : The research article effectively showcases AI’s transformative potential in healthcare, though it could be strengthened by a deeper exploration of ethical issues and more practical examples.
Title : The Psychological Effects of Social Media Use on Adolescents: A Research-Based Review Introduction : This review evaluates the research article’s examination of how social media affects adolescents’ mental health, focusing on anxiety, depression, and self-esteem. Summary : The article presents data from longitudinal studies and surveys to show the correlation between social media use and various psychological issues. It discusses the impact of online interactions, cyberbullying, and the pressure to conform to social norms. Critique : The research is detailed and presents significant findings. However, it could benefit from a more balanced view that includes positive aspects of social media, such as support networks and educational content. Additionally, the sample sizes in some studies are limited, which may affect the generalizability of the results. Conclusion : The research article provides a comprehensive overview of the negative psychological effects of social media on adolescents, though it would be improved by a more balanced perspective and larger sample sizes.
Title : The Effectiveness of Mindfulness-Based Stress Reduction Programs: A Research Review Introduction : This review analyzes the research article’s evaluation of mindfulness-based stress reduction (MBSR) programs and their impact on mental health and well-being. Summary : The article reviews various studies on MBSR, highlighting its benefits for reducing stress, anxiety, and depression. It includes meta-analyses and randomized controlled trials to provide a robust evidence base. Critique : The research is comprehensive and well-supported by empirical data. However, it could explore more on the long-term benefits and potential limitations of MBSR programs. The article would also benefit from discussing the accessibility and applicability of these programs across different populations. Conclusion : The research article effectively demonstrates the benefits of MBSR programs for mental health, though it could be enhanced by addressing long-term effects and broader applicability.
Review of “the impact of social media on academic performance”.
Title : The Impact of Social Media on Academic Performance: A Comprehensive Review Introduction : This review evaluates the journal article’s investigation into the relationship between social media usage and academic performance among students. Summary : The article discusses various studies that explore how social media affects students’ academic outcomes. It highlights both positive effects, such as improved communication and resource sharing, and negative impacts like distraction and reduced study time. Critique : The article is thorough, providing a balanced view supported by empirical data. However, it could benefit from more longitudinal studies to understand long-term effects. Additionally, the article does not address differences in impact based on the type of social media platform used. Conclusion : The journal article effectively highlights the dual impact of social media on academic performance. To strengthen the research, including more long-term studies and platform-specific analyses would be beneficial.
Title : Climate Change Adaptation in Urban Areas: An Analytical Review Introduction : This review analyzes the journal article’s discussion on how urban areas are adapting to climate change, focusing on infrastructure and policy changes. Summary : The article examines various adaptation strategies employed by cities worldwide, such as green infrastructure, zoning laws, and disaster preparedness programs. It presents case studies from different regions to illustrate successful adaptation efforts. Critique : The article is well-researched and provides a comprehensive overview of adaptation strategies. However, it could include more data on the effectiveness of these strategies over time. Additionally, the article would benefit from a discussion on the socio-economic challenges that hinder adaptation in less developed areas. Conclusion : The journal article provides valuable insights into urban climate change adaptation strategies. It would be strengthened by including long-term effectiveness data and addressing socio-economic barriers.
Title : The Role of Artificial Intelligence in Personalized Medicine: A Detailed Review Introduction : This review evaluates the journal article’s exploration of AI applications in personalized medicine, including diagnostics and treatment plans. Summary : The article discusses how AI technologies, such as machine learning and data analytics, are revolutionizing personalized medicine. It highlights examples where AI has improved diagnostic accuracy and tailored treatment plans to individual patient needs. Critique : The article is insightful and well-supported by clinical data. However, it could delve deeper into the ethical considerations and potential biases in AI algorithms. Additionally, more real-world examples of AI implementation in diverse healthcare settings would enhance the article’s applicability. Conclusion : The journal article effectively demonstrates the transformative potential of AI in personalized medicine. To improve, it should include a more detailed discussion on ethics and practical applications across different healthcare systems.
Title : The Psychological Impact of COVID-19 on Healthcare Workers: A Research Review Introduction : This review analyzes the journal article’s investigation into the mental health effects of the COVID-19 pandemic on healthcare workers. Summary : The article presents data from surveys and interviews with healthcare professionals, highlighting increased levels of stress, anxiety, and burnout due to the pandemic. It discusses the factors contributing to these psychological impacts, such as workload, exposure risk, and lack of support. Critique : The article provides a comprehensive analysis of the psychological challenges faced by healthcare workers during the pandemic. However, it could benefit from more longitudinal studies to understand long-term mental health outcomes. Additionally, the article would be improved by offering more detailed recommendations for institutional support and intervention strategies. Conclusion : The journal article effectively sheds light on the mental health struggles of healthcare workers during COVID-19. To strengthen the research, including long-term studies and detailed support recommendations would be beneficial.
Title : Sustainable Agriculture Practices and Food Security: An In-Depth Review Introduction : This review evaluates the journal article’s discussion on the role of sustainable agriculture practices in enhancing food security. Summary : The article explores various sustainable agriculture techniques, such as crop rotation, organic farming, and agroforestry, and their impact on food security. It presents case studies demonstrating how these practices can increase crop yields and improve resilience to climate change. Critique : The article is well-researched and provides a detailed analysis of sustainable agriculture practices. However, it could include more quantitative data on the economic viability of these practices for small-scale farmers. Additionally, the article would benefit from discussing the policy frameworks needed to support widespread adoption of sustainable agriculture. Conclusion : The journal article effectively highlights the importance of sustainable agriculture for food security. It would be enhanced by including more economic data and policy recommendations to support these practices.
Review of “the effects of sleep deprivation on academic performance”.
Title : The Effects of Sleep Deprivation on Academic Performance: A Detailed Review Introduction : This review assesses the article’s exploration of how sleep deprivation impacts college students’ academic performance, focusing on cognitive functions and overall well-being. Summary : The article examines studies showing that insufficient sleep negatively affects memory, concentration, and problem-solving skills, leading to lower grades and academic achievement. It also discusses the role of stress and lifestyle factors contributing to sleep deprivation. Critique : The article provides a thorough analysis supported by empirical data. However, it could benefit from a broader range of studies, including different demographic groups. Additionally, practical solutions for improving sleep habits among students are not adequately addressed. Conclusion : The article effectively highlights the critical relationship between sleep and academic performance but would be strengthened by more diverse studies and practical recommendations for students.
Title : The Impact of Technology on Modern Education: A Comprehensive Review Introduction : This review evaluates the article’s discussion on the integration of technology in higher education and its effects on teaching and learning processes. Summary : The article explores various technological tools used in education, such as online learning platforms, interactive simulations, and digital resources. It discusses the benefits, including increased accessibility and personalized learning, as well as challenges like digital divide and technological distractions. Critique : The article is well-researched and balanced, highlighting both positive and negative aspects of technology in education. However, it could include more recent data and specific examples of successful technology implementations in colleges. Additionally, the article should address potential long-term impacts on traditional teaching methods. Conclusion : The article provides valuable insights into the role of technology in education, though it would be enhanced by including more up-to-date examples and long-term impact analysis.
Title : Mental Health Awareness Among College Students: An Analytical Review Introduction : This review analyzes the article’s exploration of mental health awareness programs in colleges and their effectiveness in addressing student mental health issues. Summary : The article examines various initiatives aimed at improving mental health awareness, such as workshops, counseling services, and peer support groups. It highlights the importance of early intervention and the role of campus resources in supporting student well-being. Critique : The article provides a comprehensive overview of mental health awareness programs and their benefits. However, it could benefit from more quantitative data on program effectiveness and student outcomes. Additionally, the article should discuss the barriers to accessing mental health services, such as stigma and resource limitations. Conclusion : The article effectively underscores the significance of mental health awareness in colleges, but it would be improved by including more data on program effectiveness and addressing access barriers.
Title : The Role of Extracurricular Activities in Student Development: A Detailed Review Introduction : This review evaluates the article’s discussion on how participation in extracurricular activities impacts college students’ personal and academic development. Summary : The article explores various benefits of extracurricular activities, such as improved social skills, leadership development, and enhanced academic performance. It includes case studies and survey data to support its findings. Critique : The article is well-rounded and provides clear evidence of the positive impacts of extracurricular activities. However, it could include more diverse examples from different types of colleges and regions. Additionally, the article should address potential negative aspects, such as time management challenges and academic pressure. Conclusion : The article effectively highlights the importance of extracurricular activities in student development, though it would benefit from a more diverse range of examples and a balanced discussion of potential drawbacks.
Title : The Influence of Social Media on College Students’ Mental Health: A Research Review Introduction : This review analyzes the article’s investigation into how social media usage affects the mental health of college students, focusing on both positive and negative impacts. Summary : The article discusses various studies showing that social media can lead to increased anxiety, depression, and feelings of isolation among students. It also highlights positive aspects, such as enhanced communication, social support, and access to mental health resources. Critique : The article provides a balanced view, supported by empirical data and real-world examples. However, it could benefit from more recent studies and a deeper exploration of how different social media platforms uniquely impact mental health. Additionally, the article should include practical advice for students on managing social media use. Conclusion : The article effectively addresses the complex relationship between social media and mental health among college students, but it would be strengthened by including more recent research and practical recommendations.
Review of “the effects of microplastics on marine life”.
Title : The Effects of Microplastics on Marine Life: A Comprehensive Review Introduction : This review assesses the scientific article’s investigation into the impact of microplastics on marine organisms, focusing on ingestion, toxicity, and ecological consequences. Summary : The article presents various studies showing that microplastics are ingested by a wide range of marine species, leading to physical harm and chemical toxicity. It discusses how microplastics affect growth, reproduction, and survival rates of marine life. Critique : The article is well-researched, providing detailed evidence of the harmful effects of microplastics. However, it could benefit from a broader geographic scope, including more diverse marine environments. Additionally, the article lacks a discussion on potential mitigation strategies to reduce microplastic pollution. Conclusion : The article effectively highlights the detrimental impact of microplastics on marine life, but it would be strengthened by including a wider range of environments and discussing mitigation measures.
Title : The Role of CRISPR-Cas9 in Gene Editing: A Detailed Review Introduction : This review evaluates the scientific article’s exploration of the CRISPR-Cas9 technology and its applications in gene editing, focusing on its potential and ethical considerations. Summary : The article discusses the mechanism of CRISPR-Cas9 and its use in various fields such as medicine, agriculture, and biotechnology. It highlights successful case studies, including the treatment of genetic disorders and the development of disease-resistant crops. Critique : The article is insightful and provides a comprehensive overview of CRISPR-Cas9. However, it could delve deeper into the ethical issues and potential unintended consequences of gene editing. Additionally, the article would benefit from more recent examples of CRISPR applications. Conclusion : The article effectively demonstrates the potential of CRISPR-Cas9 in gene editing, though it could be enhanced by addressing ethical considerations and providing more up-to-date examples.
Title : Climate Change and Its Impact on Global Food Security: An Analytical Review Introduction : This review analyzes the scientific article’s examination of how climate change affects global food security, focusing on crop yields, food supply, and nutrition. Summary : The article explores various factors influenced by climate change, including temperature changes, altered precipitation patterns, and increased frequency of extreme weather events. It discusses how these factors affect agricultural productivity and food availability. Critique : The article is thorough and supported by extensive data. However, it could include more case studies from different regions to provide a global perspective. Additionally, the article would benefit from discussing adaptation strategies and policy recommendations to mitigate the impact of climate change on food security. Conclusion : The article provides valuable insights into the effects of climate change on food security, but it would be improved by including more regional case studies and discussing mitigation strategies.
Title : The Advancements in Renewable Energy Technologies: A Research Review Introduction : This review evaluates the scientific article’s discussion on the latest advancements in renewable energy technologies, including solar, wind, and bioenergy. Summary : The article highlights recent innovations in renewable energy, such as improved solar panel efficiency, advanced wind turbine designs, and sustainable bioenergy production methods. It presents data on the cost-effectiveness and environmental benefits of these technologies. Critique : The article is well-researched and presents a clear overview of advancements in renewable energy. However, it could benefit from a more detailed analysis of the challenges and limitations associated with each technology. Additionally, the article should include projections on the future adoption of these technologies. Conclusion : The article effectively showcases the progress in renewable energy technologies, though it would be enhanced by addressing challenges and providing future adoption projections.
Title : The Impact of Artificial Intelligence on Healthcare: A Comprehensive Review Introduction : This review analyzes the scientific article’s exploration of AI’s impact on healthcare, focusing on diagnostic tools, patient care, and administrative efficiency. Summary : The article discusses various AI applications in healthcare, such as machine learning algorithms for disease diagnosis, robotic surgeries, and AI-driven patient management systems. It highlights the potential benefits and challenges of AI integration in healthcare. Critique : The article is insightful and supported by clinical data. However, it could delve deeper into the ethical considerations and data privacy issues associated with AI in healthcare. Additionally, more real-world examples and case studies would enhance the article’s relevance. Conclusion : The article effectively demonstrates AI’s transformative potential in healthcare, but it would be strengthened by addressing ethical concerns and including more practical examples.
Review of “the influence of parenting styles on child development”.
Title : The Influence of Parenting Styles on Child Development: A Comprehensive Review Introduction : This review evaluates the article’s investigation into how different parenting styles affect children’s psychological and emotional development. Summary : The article explores various parenting styles—authoritative, authoritarian, permissive, and neglectful—and their impacts on children’s behavior, self-esteem, academic performance, and social skills. It presents data from longitudinal studies and surveys. Critique : The article is thorough and well-supported by empirical data. However, it could benefit from more recent studies and a broader demographic scope. Additionally, practical recommendations for parents based on the findings are not adequately addressed. Conclusion : The article effectively highlights the significant role of parenting styles in child development. It would be strengthened by including more up-to-date research and practical advice for parents.
Title : The Effects of Social Media on Adolescent Mental Health: A Detailed Review Introduction : This review analyzes the article’s exploration of the psychological effects of social media use on adolescents, focusing on issues like anxiety, depression, and self-esteem. Summary : The article discusses various studies that show a correlation between social media use and increased rates of mental health issues among adolescents. It examines factors such as cyberbullying, social comparison, and screen time. Critique : The article provides a balanced view supported by empirical data. However, it could include more recent studies and a deeper exploration of positive aspects of social media, such as support networks and educational content. Additionally, practical strategies for managing social media use are not sufficiently addressed. Conclusion : The article effectively discusses the negative impacts of social media on adolescent mental health but would benefit from more recent research and practical recommendations.
Title : Cognitive Behavioral Therapy for Treating Depression: An Analytical Review Introduction : This review evaluates the article’s discussion on the effectiveness of cognitive behavioral therapy (CBT) in treating depression, focusing on clinical outcomes and patient experiences. Summary : The article reviews various studies demonstrating CBT’s effectiveness in reducing depressive symptoms and preventing relapse. It discusses CBT’s core components, including cognitive restructuring and behavioral activation. Critique : The article is well-researched and provides a comprehensive overview of CBT’s effectiveness. However, it could benefit from more detailed comparisons with other therapeutic approaches and a discussion on the accessibility and scalability of CBT. Additionally, the article should address potential limitations and criticisms of CBT. Conclusion : The article effectively showcases CBT’s effectiveness in treating depression, though it would be enhanced by including comparisons with other therapies and addressing accessibility issues.
Title : The Role of Mindfulness Meditation in Stress Reduction: A Research Review Introduction : This review analyzes the article’s examination of mindfulness meditation as a technique for reducing stress and improving mental health. Summary : The article discusses various studies that show how mindfulness meditation can reduce stress, anxiety, and depressive symptoms. It explains the underlying mechanisms, such as increased self-awareness and emotional regulation. Critique : The article is insightful and supported by empirical data. However, it could include more longitudinal studies to understand the long-term effects of mindfulness meditation. Additionally, the article should address potential barriers to practicing mindfulness, such as time constraints and individual differences in response to meditation. Conclusion : The article effectively highlights the benefits of mindfulness meditation for stress reduction but would be improved by including long-term studies and discussing barriers to practice.
Title : The Impact of Sleep on Cognitive Function: A Comprehensive Review Introduction : This review evaluates the article’s investigation into the relationship between sleep and cognitive function, focusing on memory, attention, and problem-solving skills. Summary : The article presents various studies demonstrating that adequate sleep is crucial for optimal cognitive performance. It discusses how sleep deprivation negatively affects cognitive functions and the underlying biological mechanisms involved. Critique : The article is thorough and well-supported by empirical data. However, it could benefit from a more detailed exploration of the differences in sleep needs across different age groups and a discussion on strategies to improve sleep quality. Additionally, practical recommendations for individuals suffering from sleep disorders are not adequately addressed. Conclusion : The article effectively highlights the critical role of sleep in cognitive function but would be strengthened by including more age-specific research and practical advice for improving sleep quality.
Article reviews are critical assessments of scholarly articles, often used to evaluate the quality, relevance, and significance of the research. Understanding the different types of article reviews helps in identifying the purpose and approach suitable for various academic and professional needs. Here are the main types of article reviews:
A narrative review provides a comprehensive summary of literature on a specific topic. It focuses on discussing the findings of the research studies and offers a narrative explanation of the trends and themes.
Characteristics:
Example: Reviewing literature on the impact of social media on mental health.
A systematic review is a methodical and comprehensive literature review that aims to answer a specific research question. It uses systematic methods to collect secondary data, critically appraise research studies, and synthesize findings.
Example: Evaluating the effectiveness of different interventions for reducing hypertension.
A meta-analysis is a statistical technique that combines the results of multiple studies to identify overall trends and determine the effectiveness of interventions.
Example: Combining data from various studies on the effectiveness of cognitive-behavioral therapy for anxiety.
A critical review evaluates the strengths and weaknesses of a scholarly article. It involves analyzing the methodology, arguments, evidence, and contributions of the article.
Example: Critiquing the research design and conclusions of a study on climate change impacts on agriculture.
A literature review surveys books, scholarly articles, and other sources relevant to a particular issue, area of research, or theory, providing a description, summary, and critical evaluation of these works.
Example: Reviewing literature on renewable energy sources and their environmental impacts.
A scoping review maps the key concepts underpinning a research area and the main sources and types of evidence available. It aims to provide an overview of the range of research activity.
Example: Exploring the range of studies on artificial intelligence applications in healthcare.
An integrative review synthesizes theoretical and empirical literature to provide a more comprehensive understanding of a specific phenomenon or healthcare problem.
Example: Integrating research on patient-centered care models in nursing.
A conceptual review focuses on theories and concepts in a particular field. It examines how these concepts are defined, measured, and applied in the literature.
Example: Reviewing the evolution of the concept of resilience in psycholog
1. formal article review.
An article review involves evaluating and summarizing a scholarly article, presenting critical insights, and reflecting on its implications. Understanding the essential components helps in crafting a thorough and insightful review. Here are the key components:
Example: “Review of ‘The Impact of Social Media on Mental Health’ by John Smith”
The article “The Impact of Social Media on Mental Health” by John Smith explores the relationship between social media usage and mental health outcomes. This review aims to critically evaluate the article’s findings and discuss its implications for future research.
The article investigates both positive and negative effects of social media on mental health. Using a mixed-methods approach, the study finds that while social media can enhance social support and community building, it also contributes to anxiety, depression, and cyberbullying.
The article provides a balanced view of social media’s impact, effectively synthesizing current research. However, it lacks in-depth analysis of the methodologies used, which could affect the validity of the findings. Future research should include longitudinal studies to better understand causal relationships.
In conclusion, Smith’s article offers valuable insights into the complex relationship between social media and mental health. While the study is comprehensive, addressing methodological limitations in future research would enhance our understanding of this important issue.
As a student, I find the article’s discussion on the negative impacts of social media particularly relevant. It underscores the importance of mindful social media use to maintain mental well-being. This review has deepened my understanding of the subject and will inform my future research.
Example: Smith, J. (2023). The Impact of Social Media on Mental Health. Journal of Psychological Studies, 45(2), 123-145.
Writing an article review involves summarizing and critically evaluating a scholarly article. This process helps in understanding the article’s contributions and limitations, and it enhances critical thinking skills. Follow these steps to write an effective article review:
The article “The Impact of Social Media on Mental Health” by John Smith explores the relationship between social media usage and mental health outcomes. This review aims to critically evaluate Smith’s findings and discuss their implications for future research.
Smith’s article investigates both positive and negative effects of social media on mental health. Using a mixed-methods approach, the study finds that social media can enhance social support and community building but also contributes to anxiety, depression, and cyberbullying.
The article provides a balanced view of social media’s impact, effectively synthesizing current research. However, it lacks an in-depth analysis of the methodologies used, which could affect the validity of the findings. Future research should include longitudinal studies to better understand causal relationships.
Smith, J. (2023). The Impact of Social Media on Mental Health. Journal of Psychological Studies, 45(2), 123-145.
Begin with a brief introduction that provides context, states the purpose of your review, and mentions the article’s title and author.
Summarize the main points of the article, including the research question, methodology, findings, and conclusions without inserting personal opinions.
Evaluate the strengths and weaknesses of the article, analyze the methodology and evidence, and discuss the significance and implications of the findings.
The length varies, but typically an article review is 2-4 pages, balancing summary, critical analysis, and personal reflection.
Summarize the key points of your review, restate the article’s significance, and provide final thoughts and suggestions for future research.
A summary restates the article’s main points objectively, while a critique evaluates the article’s strengths, weaknesses, and overall contribution.
Discuss how the article relates to your own experiences or studies and describe how it influenced your understanding of the topic.
Use direct quotes sparingly, only when they enhance your analysis. Always explain their relevance to your critique.
Follow the appropriate citation style (e.g., APA, MLA) to include a full citation of the article at the end of your review.
Yes, but primarily in the critical analysis and personal reflection sections. Ensure your opinions are supported by evidence from the article.
Text prompt
10 Examples of Public speaking
20 Examples of Gas lighting
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2021, Article review writing format, steps, examples and illustration PDF Compiled by Mohammed Yismaw
The purpose of this document is to help students and researchers understand how a review of an academic journal is conducted and reported in different fields of study. Review articles in academic journals that analyze or discuss researches previously published by others, rather than reporting new research results or findings. Summaries and critiques are two ways to write a review of a scientific journal article. Both types of writing ask you first to read and understand an article from the primary literature about your topic. The summary involves briefly but accurately stating the key points of the article for a reader who has not read the original article. The critique begins by summarizing the article and then analyzes and evaluates the author’s research. Summaries and critiques help you learn to synthesize information from different sources and are usually limited to two pages maximum.
Harald von Kortzfleisch , Christoph Kahle
Neue Technologien und Innovationen stellen heutzutage wichtige Schlüsselelemente der Wachstums und Erfolgssicherung von Unternehmen dar. Durch einen in Geschwindigkeit und Intensität immer schneller zunehmenden Wettbewerb nehmen Innovationen eine immer zentralere Rolle im Praxisalltag von Unternehmen ein. Dieser technische Fortschritt treibt auch in der Wissenschaft das Thema des Innovationsmanagements in den letzten Jahrzehnten immer stärker voran und wird dort ausgiebig diskutiert. Die Bedeutung von Innovationen wächst dabei ebenfalls aus der Sicht der Kunden, welche heutzutage viel differenzierter als früher Produkte und Dienste nachfragen und somit Unternehmen vor neue Herausforderungen stellen. Ãberdies stellen Innovationen heute ein entscheidendes Bindeglied zwischen Marktorientierung und erhofften Unternehmenserfolg dar. Seit einigen Jahren lässt sich eine Ãffnung der Unternehmensgrenzen für externe Quellen wie Kunden, Zulieferer, Universitäten oder teilweise auch M...
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Firms tap into user knowledge to learn about the users’ needs. While users have been recognized as a valuable source of knowledge for innovation, few studies have investigated how their knowledge is integrated into innovation processes in the context of complex products and systems (CoPS). The purpose of this study is to reveal the practices of CoPS manufacturers to facilitate user knowledge utilization for innovation. We investigate two case companies, a medical device manufacturer and an aircraft manufacturer, and report on seven managerial practices for utilizing user knowledge. We adopt the absorptive capacity model in structuring our findings and elaborate three of the model's sub-capabilities (recognition of the value of user knowledge, acquisition of user knowledge, and assimilation/transformation of user knowledge) by proposing that each is associated with a distinct managerial goal and related practices: (1) Sensitizing the organization to the innovation potential of user knowledge, (2) identifying and gaining access to suitable user knowledge, and (3) analyzing and interpreting user knowledge and integrating it into product development. Our study contributes to the innovation management literature by analyzing the capabilities required to utilize user knowledge throughout the CoPS innovation process.
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Diffusion of digital technologies into the manufacturing industry has created new opportunities for innovation that firms must address to remain competitive. We investigate the role of customer and user knowledge in the digital innovation processes of three global B2B manufacturing companies. We find that the B2B manufacturing industry's characteristics influence how users and customers may be leveraged. Customers making the purchasing decisions are considered for knowledge about short-term changes in market needs, while users working directly with the products provide long-term guidance for digital innovation. We identify practices for acquiring, distributing, and using customer and user knowledge for digital innovation.
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Journal of Entrepreneurship, Management and Innovation JEMI
Given the rising role of users in innovation processes and the increasing amount of research in this field the aim of this paper is to explore the limits of our understanding of the user innovation (UI) concept. In doing so, the study addresses four basic questions: (1) Why do users create and share innovation? (2) Who is the user-innovator? (3) What type of innovation do users create? (4) How do users innovate? The results of a systematic literature review identified the main research streams on user innovation, together with weaknesses of past research and perspectives for future studies.
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The term “peer review” was coined in the 1970s, but the referee principle is usually assumed to be as old as the scientific enterprise itself. (It isn’t.)
Peer review has become a cornerstone of academic publishing, a fundamental part of scholarship itself. With peer review, independent, third-party experts in the relevant field(s) assess manuscripts submitted to journals. The idea is that these expert peers referee the process, especially when it comes to technical matters that may be beyond the knowledge of editors.
“In all fields of academia, reputations and careers are now expected to be built on peer-reviewed publication; concerns with its efficacy and appropriateness thus seem to strike at the heart of scholarship,” write historians Noah Moxham and Aileen Fyfe .
The peer review system, continue Moxham and Fyfe, is “crucial to building the reputation both of individual scientists and of the scientific enterprise at large” because the process
is believed to certify the quality and reliability of research findings. It promises supposedly impartial evaluation of research, through close scrutiny by specialists, and is widely used by journal editors, grant-making bodies, and government.
As with any human enterprise, peer review is far from foolproof . Errors and downright frauds have made it through the process. In addition, as Moxham and Fyfe note, there can be “inappropriate bias due to the social dynamics of the process.” (Some peer review types may introduce less bias than others.)
The term “peer review” was coined in the early 1970s, but the referee principle is usually assumed to be about as old as the scientific enterprise itself, dating to the Royal Society of London’s Philosophical Transactions , which began publication in 1665.
Moxham and Fyfe complicate this history, using the Royal Society’s “rich archives” to trace the evolution of editorial practices at one of the earliest scientific societies.
Initially, the publication of Philosophical Transactions was a private venture managed by the Society’s secretaries. Secretary Henry Oldenburg, the first editor, ran it from 1665 to 1677, without, write Moxham and Fyfe, any “clear set of standards.”
Research sponsored by the Royal Society itself was published separately from the Transactions . In fact, the royally chartered Society had the power to license publication of books and periodicals (like the Transactions ) as “part of a wider mechanism of state censorship intended to ensure the proscription of politically seditious or religious heterodox material.” But as time passed, there wasn’t really much Society oversight over the publication at all.
The situation came to a crisis in the early 1750s, when an unsuccessful candidate for a Society fellowship raised a ruckus, conflating the separate administrations of the Society and the now rather stodgy Transactions. The bad press compelled the Society to take over financial and editorial control—by committee—of the Transactions in 1752. The editorial committee could refer submissions to fellows with particular expertise—but papers were already being vetted since they needed to be referred by fellows in the first place.
Formalization of the use of expert referees would be institutionalized by 1832. A “written report of fitness” of submissions by one or more fellows was to be made before acceptance. This followed similar procedures already introduced abroad, particularly at the Académie des sciences in Paris.
All of this, Moxham and Fyfe argue, was more about institution-building (and fortification) than what we know as peer reviewing today.
“Refereeing and associated editorial practices” were intended to “disarm specific attacks upon the eighteenth-century Society; sometimes, to protect the Society’s finances; and, by the later nineteenth century, to award prestige to members of the nascent profession of natural scientists.”
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From 1752 to 1957, the front of every Transactions included an “ Advertisement ” noting that the Society could not pretend to “answer for the certainty of the facts, or propriety of the reasonings” of the papers contained within; all that “must still rest on the credit or judgement of their respective authors.”
The twentieth century saw a plethora of independent scientific journals and an exponential increase in scientific papers. “Professional, international scientific research” burst the bounds of the old learned societies with their gentlemanly ways. In 1973, the journal Nature (founded in 1869) made refereeing standard practice, to “raise the journal above accusations of cronyism and elitism.” Since then, peer review, as it came to be called in preference to refereeing, has become universal. At least in avowed “peer-reviewed journals.”
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Journal articles are the academic's stock in trade, t he basic means of communicating research findings to an audience of one’s peers. That holds true across the disciplinary spectrum, so no matter where you land as a concentrator, you can expect to rely on them heavily.
Regardless of the discipline, moreover, journal articles perform an important knowledge-updating function .
Textbooks and handbooks and manuals will have a secondary function for chemists and physicists and biologists, of course. But in the sciences, articles are the standard and preferred publication form.
In the social sciences and humanities , where knowledge develops a little less rapidly or is driven less by issues of time-sensitivity , journal articles and books are more often used together.
Not all important and influential ideas warrant book-length studies, and some inquiry is just better suited to the size and scope and concentrated discussion that the article format offers.
Journal articles sometimes just present the most appropriate solution for communicating findings or making a convincing argument. A 20-page article may perfectly fit a researcher's needs. Sustaining that argument for 200 pages might be unnecessary -- or impossible.
The quality of a research article and the legitimacy of its findings are verified by other scholars, prior to publication, through a rigorous evaluation method called peer-review . This seal of approval by other scholars doesn't mean that an article is the best, or truest, or last word on a topic. If that were the case, research on lots of things would cease. Peer review simply means other experts believe the methods, the evidence, the conclusions of an article have met important standards of legitimacy, reliability, and intellectual honesty.
Searching the journal literature is part of being a responsible researcher at any level: professor, grad student, concentrator, first-year. Knowing why academic articles matter will help you make good decisions about what you find -- and what you choose to rely on in your work.
Think of journal articles as the way you tap into the ongoing scholarly conversation , as a way of testing the currency of a finding, analysis, or argumentative position, and a way of bolstering the authority (or plausibility) of explanations you'll offer in the papers and projects you'll complete at Harvard.
Except where otherwise noted, this work is subject to a Creative Commons Attribution 4.0 International License , which allows anyone to share and adapt our material as long as proper attribution is given. For details and exceptions, see the Harvard Library Copyright Policy ©2021 Presidents and Fellows of Harvard College.
BMC Medical Research Methodology volume 24 , Article number: 159 ( 2024 ) Cite this article
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The story completion method provides a different way of doing qualitative research. We note the emergent popularity of this method in health-related research, while much remains to be negotiated in terms of best practices for such studies. This scoping review aims to provide a synthesis on how researchers have used the story completion method in health services research. We offer implications for research and practice for further discussion by the scholarly community.
We used the JBI methodology for scoping reviews. Six databases were searched for published literature till March 1, 2023: Medline, Embase, CINAHL, PsycINFO, SAGE Journals Online databases, and SAGE Research Methods. We included primary studies of any study design using the story completion method in health services research.
A total of 17 studies were included. Findings suggest that the story completion method is useful for research on sensitive topics, and affords the use of comparative study designs and large sample sizes which may be difficult with conventional qualitative research methods. More than 80% of included studies used story completion as the sole method. However, the data collected from this method were limited in terms of the inferences that can be drawn; and richness of participant responses may vary widely. Less than 30% of included studies reported piloting of the story stems. Most studies were conducted online and analyzed qualitatively, though the story stem design and sample size varied widely.
The story completion method, with its attendant affordances for larger sample sizes, comparative study designs, and streamlined data collection is an innovative and useful stand-alone or adjunct qualitative method for health services research.
Peer Review reports
Qualitative methods increasingly underpin robust population health research, health services research, and implementation research [ 1 , 2 , 3 ]. The insights provided by qualitative methods allow us to appropriately design, execute, and evaluate a plethora of healthcare programs and innovations, including digital health and AI-augmented healthcare [ 4 , 5 , 6 ].
Qualitative methods used in these fields include interviews and focus groups. These methods are often time and resource intensive [ 7 ], and arguably less efficacious in eliciting uncensored views especially for topics that are socio-culturally sensitive [ 8 ]. In that, participants may adjust their positions on an issue to align with what they perceive as accepted social or cultural discourses, perhaps to avoid potential repercussions [ 9 ].
Story completion is a method not often used in population health, health services, and implementation research. Given its attributes, apart from being used on its own to explore socio-culturally sensitive topics, story completion promises to be a useful adjunct to semi-structured interviews and focus groups. The story completion method has already garnered much interest in the scholarly community, with several published discussions regarding its utility and issues [ 10 , 11 ], flexibility as a method across disciplines [ 12 ], and potential for decolonizing research methodologies [ 13 ].
Story completion, first used in quantitative developmental psychology research and in psychoanalysis as a projective technique for clinical assessment, was subsequently re-developed as a qualitative method by Kitzinger for feminist research [ 8 ]. Importantly, Kitzinger re-conceptualized story completion in the mid-1990s as a way “to access not just psychological meanings but also social discourses” [ 8 ]. More recently, Clarke and colleagues re-ignited interest in this method with the publication of a special issue “Using Story Completion Methods in Qualitative Research” in the Qualitative Research in Psychology journal [ 8 ]. Although story completion originated as a pen-and-paper task, this method has been increasingly administered online. Hence, the moniker, digital story completion.
In typical story completion studies, participants are presented with one or several hypothetical scenarios that act as writing prompts (story stems) and asked to complete the story however they like (Table 1 ). In example 1, researchers used story completion as a stand-alone qualitative method to collect narratives from Australian adults regarding their views on the COVID-19 restrictions implemented, and how it affected their health and well-being [ 14 ]. The story completion method was chosen due to its ability to examine social discourses, meanings, norms, and assumptions; and researchers were interested to understand how individuals would react to constantly changing situations, such as COVID-19 restrictions [ 14 ]. In example 2, researchers also used story completion as a stand-alone method to explore how evangelical Christians perceive depression [ 15 ]. Story completion method was chosen in this case due to the stigma associated with depression or mental health in general; and as this method does not explicitly obtain respondents’ personal experiences or views, it reduces the risk of social desirability bias [ 15 ].
A key advantage of the story completion method is its ability to side-step solely direct personal experiences to include socio-cultural discourse and representations, which enables researchers to understand meaning-making frameworks of a particular social group [ 10 ]. Other notable advantages of the method include the ability to accommodate larger samples of participants relative to traditional qualitative methods, and the contentious use of comparative study designs, uncommon in qualitative research [ 10 ].
A perceived weakness of this method has to do with the invitation to participants to be imaginative when responding to the story stem, triggering some researchers (and users of research) to be concerned that “anything goes.” To alleviate this concern, we recognize the bi-directional connection between imagination and experience, where imagination is influenced by an individual’s experiences [ 16 ] and “experiences are partly constituted through the stories within [one’s] socio-cultural landscapes [ 17 ]. So, despite its apparent playfulness, story completion holds merit as a sole method and as a useful adjunct to traditional qualitative methods in multiple- or mixed-methods studies.
We observed a steady increase via PubMed in the number of studies using story completion for health-related research in the last five years. While each study justifies and explains its use, it is our opinion that much needs to be clarified and negotiated about best practices for this method. For example, how should story stems be derived? How and when to use comparator groups? How large should the sample be to yield adequate data for meaningful analysis? These questions pertain to future discussions about best practices or ‘shoulds’. However, we first need to understand the current landscape. In this scoping review we elicited how the story completion method has been used in health-related research. Specifically, we were interested in: (a) the target populations and/or health conditions, (b) the study designs used, (c) how story stems were derived, (d) how data were analyzed, (e) other research methods used to triangulate data from the story completion method, and (f) strengths and weaknesses of the method stated by study authors. Our findings serve as a useful resource or starting point for health services researchers interested in using the story completion method, when planning or designing their study.
This study was carried out in accordance with the JBI methodology for scoping review [ 18 ]. The protocol was published on Open Science Framework (available here: https://osf.io/rk2e6/ ) [ 19 ]. We developed a search strategy using the PRESS guidelines [ 20 ] and consulted university librarians for refinement around the following key terms: story completion and health services research (Additional File 1 ). We searched six databases: Medline, Embase, CINAHL, PsycINFO, SAGE Journals Online databases, and SAGE Research Methods for published literature till March 1, 2023.
Inclusion criteria: a primary study of any study design using the story completion method in health services research. For the purposes of this review, we defined story completion as a type of qualitative research method where study participants are asked to complete a story based on an assigned story “stem” or opening [ 8 ], and health services research as an interdisciplinary study of scientific investigation that explores how social determinants, financial policies, organizational systems and structures, medical technology, and individual actions influence cost, access, quality of healthcare, and also our well-being and health [ 21 ]. This definition of health services research does not confine it to the provision of health services or health structures, but also includes the exploration of how social determinants and individual behaviors affect health and well-being. The World Health Organization recognizes social determinants such as social exclusion and discrimination as important factors that can affect access to healthcare and health equity in negative ways [ 22 ]. Hence, studies investigating perceptions of potentially stigmatizing conditions or sexual orientations which are likely to influence how/whether those individuals seek help/healthcare have been included. Studies were excluded if they were editorials, commentaries, discussion papers, methodological papers (non-empirical), conference papers, systematic reviews, meta-analyses, or study protocols.
Three researchers (CP, NJR, EL) independently conducted title/abstract and full text screening of studies captured by the search strategy. Conflicts at both screening stages were resolved through discussion by two lead researchers (NJR, EL). Covidence ® , a web-based software for conducting reviews (Veritas Health Innovation, Melbourne, Australia) and Endnote 20 (Clarivate Analytics, PA, USA) were used for screening and managing citations respectively. Studies in languages other than English were translated using ChatGPT (OpenAI, CA, USA) and screened by two researchers (CP, EL), to determine eligibility.
A standardized form was developed for data extraction using Google Forms. The following data were extracted: publication year, author, country of study, characteristics of the study population, study aim(s), study design, description of the story completion study, sample size, how story stems were derived, how data was captured and analyzed including type of analysis (e.g. Braun & Clarke’s reflexive thematic analysis, etc.), other research methods used to triangulate data (e.g. semi-structured interviews, surveys, focus groups, etc.), reported strengths and weaknesses of the story completion method, assumptions and underlying theories.
The form was piloted by three researchers (CP, NJR, EL) using three included studies, and refined accordingly. How we operationalized data extraction is shown in Additional File 2 . Two researchers (CP, EL) independently completed data extraction for the remaining studies. Publication year and sample size were extracted as numerical values. Other data points expressed as textual data were summarized rather than extracted verbatim from included studies, apart from author, country of study, and study aims. For example, data point “characteristics of the study population” were summarized as “Australia-based adults aged 18 and above during the COVID-19 pandemic”, “adolescents aged 14–25 years old with complex regional pain syndrome” and so forth. Descriptive statistics, where appropriate, were used to summarize extracted data in Excel ® (Version 1808 (Microsoft)). For example, to provide a numerical count of how many included studies were single country versus multi-country, and so forth.
The search yielded 278 studies. After removing 75 duplicates, 203 studies remained for screening. At full text screening stage there were nine studies reported in languages other than English which were translated using ChatGPT; these did not meet eligibility criteria and were excluded. A total of 17 studies were included in this review (Fig. 1 ). The list of included studies is provided as Additional File 3 .
PRISMA-scoping review flow diagram [ 18 ]
The main characteristics of included studies are summarized in Table 2 . The majority were single country studies (15/17, 88·2%), originating from the European region (9/17, 52·9%) and Western Pacific region (4/17, 23·5%). Most of the studies were published between 2021 and 2023 (9/17, 52·9%). In terms of the study design used, of the 17 studies, 13 (76·5%) were qualitative, three (3/17, 17·6%) used a mixed-method design, and one (1/17, 5·9%) used a multi-method design (Table 2 ). We used the following definitions for mixed-method and multi-method studies, respectively. Mixed-method studies use two or more methods in a single research project comprising both qualitative and quantitative approaches, that involves the connection, integration, or linking of these two approaches [ 23 ]. Multi-method studies use two or more solely qualitative or solely quantitative methods in a single research project [ 24 ]. In addition, although the story completion method allows for comparative study designs, this was adopted by only three studies (3/17, 17·6%) [ 25 , 26 , 27 ].
Most studies asked participants to complete one story stem each, with the exception of five studies (5/17, 29·4%) which asked each participant to complete either two [ 30 , 31 , 32 ] or three story stems [ 33 , 34 ]. Of these five studies, four provided multiple story stems to allow a diversity of illnesses, genders, socio-economic groups, or occupations to be included in the stem [ 30 , 32 , 33 , 34 ]; while one did not provide a rationale for having multiple stems. Story stems provided were fairly brief, consisting of two to five short sentences. Examples of story stems can be found in Table 1 .
For single story stem studies ( n = 12), most provided the same story opening to every participant, except three (3/12, 25.0%) which adopted a comparative design where study authors developed two story stems of the same narrative but with different protagonists in terms of gender [ 25 , 26 ] or occupation [ 27 ]. Participants were allocated [ 25 ] or randomly allocated to either stem [ 26 , 27 ]. Another study (1/12, 8.3%) randomized each participant to one of three story stems pertaining to the research, with results from each stem analyzed separately [ 35 ]. Of the five multi-story stems studies, three (3/5, 60.0%) provided the story openings in the same order for participants [ 31 , 33 , 34 ]. Two studies (2/5, 40.0%) counterbalanced the order of the story openings with half the participants presented with the first story stem followed by the second story stem while the other half were presented with the second story stem followed by the first [ 30 , 32 ].
Most studies provided participant guidelines for either time (minutes) and/or length (number of words/ characters/ sentences) for story responses (10/17, 58·8%), though these varied widely among studies (Table 3 ). Sample size varied widely among studies as well; ranging from 17 to as large as 227 (Table 3 ).
Study aims, populations studied, and health conditions are shown in Table 3 . Study participants were recruited from general populations or subgroups of general populations (e.g. adolescents, gay men), or were working adults in the healthcare industry and/or students in a health-related course. Most studies targeted a particular health condition (13/17, 76·5%). Of those that did, six studies focused on mental health conditions (6/17, 35·3%), three on chronic diseases (3/17, 17·6%), and one on cancer (1/17, 5·9%).
Study aims of some included studies are socio-culturally sensitive. For example, in the study by Lloyd et al 2022 one of the aims was to “explore how self-harm is perceived” [ 36 ], while Walsh et al 2010 aimed to “explore the ways in which ‘anorexic’ and ‘bulimic’ young women are discursively constructed by those who neither self-identify as ‘eating disordered’ nor are involved in ‘eating disorder’ interventions” [ 32 ].
Story stems were constructed by study authors in most studies, except for four studies (4/17, 23.5%) where study authors reported using either published literature or a theoretical framework to inform the development of story stems [ 27 , 33 , 36 , 37 ], and one study (1/17, 5.9%) which derived and modified the story stems based on the Wallace (1956) measure [ 31 , 38 ]. The Wallace measure estimates how far into the future a person typically plans (future time perspective) and consists of two types of questions concerning timeframes about future actions or outcomes [ 38 ]. For example, the first type of question may ask participants to list 10 events that will occur in their lives and the age they would expect to be for each event. The second type of question asks participants to write endings to story stems (i.e. story completion) and to indicate the duration in which the story occurred (e.g. “x” minutes, days, years).
The majority of studies did not pre-test the story stems (12/17, 70·6%); of those that did, they were either piloted to ensure clarity [ 15 , 30 , 35 , 36 ] or to prevent potential narrowing of responses [ 9 ]. Most studies adopted third-person story stem(s), except two studies (2/17, 11.8%) that used a first-person story stem to allow participants to reflect on their perceived future [ 39 , 40 ].
Twelve out of 17 studies (70·6%) administered the story completion task online. The remaining five studies (5/17, 29.4%) were administered either in-person [ 31 , 34 ], a combination of both in-person and online [ 9 ], or did not report the mode of data collection [ 30 , 32 ]. Most studies analyzed the data qualitatively (14/17, 82·4%), with Braun & Clarke’s reflexive thematic analysis [ 41 ] as the most commonly used approach (12/17, 70·6%) (Table 2 ). However, three studies (3/17, 17.6%) applied a quantitative approach to the analysis of story completion data, as follows. The study by Nimbley et al. 2021 analyzed the stories collected using the Linguistic Inquiry and Word Count (LIWC) program which identified and coded words against pre-selected categories pertaining to positive or negative emotions, social, and cognitive dimensions determined by study authors [ 39 ]. The LIWC program subsequently generated quantitative data in the form of frequencies (counts) and proportions of words against these categories, which were further analyzed using statistical programs such as SPSS [ 39 ]. In the study by Jones et al. 2009, participants were asked to complete two story stems and to also indicate the duration in which the story occurred (e.g. minutes, days, years). The duration was quantitatively analyzed (salient to their research question), while the stories collected were not subjected to further analysis [ 31 ]. The study by Tichenor et al. 1977 analyzed the stories collected via deductive coding using a schema of 12 categories pre-developed by study authors, then assigning a frequency score [ 34 ]. The rates of expression for each of these categories were standardized through dividing the frequency scores by the number of words written by participants and multiplying this number by a constant of 1000 [ 34 ].
The majority of studies did not use other research methods to triangulate the data from the story completion method, with the exception of two (2/17, 11.8%) that used surveys [ 30 , 34 ] and one that used semi-structured interviews (1/17, 5·9%) [ 40 ]. Of the two studies that used surveys to triangulate data, one conducted the survey prior to the story completion task [ 30 ] whilst the other did not specify the order in which the tasks were carried out [ 34 ]. The sole study that used semi-structured interviews conducted them after the story completion task to explore the stories crafted by participants in greater detail [ 40 ].
The story completion method is reported to be useful for exploring sensitive topics and vulnerable populations [ 9 , 15 , 25 , 32 , 36 , 37 , 42 ] as it does not require participants to reveal their personal experiences [ 14 , 27 , 33 ]. Instead of actual behaviors, story completion method uncovers participants’ unconscious and subconscious patterns and ways of sense-making as well as perceptions towards a given scenario, beyond their lived experiences [ 9 , 14 , 15 , 27 , 35 , 42 ], thereby reducing the risk of social desirability bias [ 15 , 36 ].
Hence, this method reportedly allows study authors the potential to obtain rich data pertaining to both individual and collective experiences of major social events and problems [ 14 , 30 ] that may not be elicited through more conventional data collection methods [ 26 , 27 ]. Additionally, data from a larger group of participants can be collected more efficiently, relative to other forms of qualitative methods [ 26 , 40 ].
However, the story completion method is not without weaknesses. Study authors discerned that as the story completion method does not explicitly obtain participants’ personal experiences [ 15 , 27 , 36 ], it limits the inferences that can be derived from the findings [ 14 , 37 ]. When crafting responses, participants may exaggerate the protagonist’s life to produce a “good” story that they would otherwise not have done in a more conventional data collection method [ 32 ] or orientate their responses to include more social elements than what they would have otherwise given due to the type of story stem provided [ 40 ].
Additionally, study authors reported that participants’ engagement with the story stem varied widely. Some would provide complex and detailed responses while others produced superficial and short stories [ 25 ], and some may misinterpret the task and provide a theoretical account of the assigned story opening instead of completing the story [ 25 , 26 ]. Study authors also noted that in common with other qualitative research, it is hard to recruit male participants [ 26 ].
Most studies specified the ontology, epistemology, or theoretical lens used (10/17, 58·8%). The top three were social constructionism (4/17, 23·5%), critical realism (2/17, 11·8%), and epistemic contextualism (2/17, 11·8%) (Table 2 ). Study authors deemed the story completion method to be compatible with their selected underpinning philosophy, which was in turn used to inform interpretation of the narratives collected.
This scoping review provides a synthesis of how the story completion method has been used in health services research thus far. Our findings serve as a useful resource for health services researchers interested in exploring and using the story completion method, when planning or designing their study. We found several distinct advantages of the story completion method, suggesting its usefulness as either a sole or adjunct approach to undertaking qualitative research, provided its shortcomings are mitigated.
First, the story completion method enables large sample sizes as the collection of data can be done in a relatively efficient way, compared to traditional qualitative methods such as semi-structured interviews. Several studies included in this scoping review reported sample sizes of over 100 [ 9 , 15 , 26 , 31 , 36 , 37 ], the largest being 227 [ 31 ]. In contrast, the average sample size was between 18 and 45 in a recent systematic analysis of sample sizes for interview-based studies published over a 15-year period in health research journals [ 43 ]. Second, the story completion method can accommodate comparative study designs, which is unusual in qualitative methods, and useful for systematically eliciting differences in variables salient to the research question (e.g. male/female, novice/expert, and so forth). An overview of the story completion method by Clarke et al. 2019 underscores that this advantage allows a more “nuanced understanding of how a particular phenomenon is socially constructed” [ 8 ]. Third, story completion is especially appropriate for research on sensitive topics as it minimizes the risk of social desirability bias, a common problem reported in qualitative health research literature [ 44 ]. This is because in contrast to qualitative methods such as semi-structured interviews, the story completion method allows participants to respond to socio-culturally sensitive topics as a third party and to participate anonymously (assuming the story stem references a third party e.g. “Tom”, “Ali”, and data collection was conducted via an online platform). In our review, conditions that carry social stigma such as mental health issues and eating disorders, were target health conditions among included studies.
The shortcomings of the story completion method reported by study authors are acknowledged in methodological discussions about this innovative approach [ 10 , 11 ]. The non-intrusive data collection afforded by the story completion method might limit the inferences study authors can draw from the findings as responses might not reflect participants’ lived experiences [ 14 , 15 , 27 , 36 , 37 ]. However, Clarke et al. 2019 cautions that whether this constitutes a problem depends on the ontological stance taken: “Essentialist/realist/(post)positivist researchers may be concerned that data may not reflect or predict “real-life” behaviour. By contrast, for social constructionist or critical realist researchers interested in the sociocultural meanings or discourses people draw on when writing their stories, this critique holds no water” [ 8 ].
Additionally, story completion is a fixed self-administered task unlike other qualitative research methods such as semi-structured interviews or focus groups where researchers and participants interact to co-shape the research-in-progress. Hence, some participants may misinterpret the task [ 25 , 26 ] or provide responses that fall short of the study authors’ requirements or expectations. When confronted with such data, researchers need to judge whether these responses are sufficiently meaningful to warrant inclusion in the dataset for analysis [ 11 ]. Misinterpretation of the story completion task can be mitigated by piloting to ensure clarity [ 15 , 30 , 35 , 36 ] or to prevent potential narrowing of responses [ 9 ]. Yet, piloting of story stems was conducted by less than a third of included studies.
We note that most studies used story completion as the sole method rather than as an adjunct method. For example, other quantitative or qualitative research methods were not used to triangulate data from the story completion method. Admittedly, some research questions may not require more than a single method. However, the wider literature recognizes the potentially complementary pairing of the story completion method with another method such as semi-structured interviews [ 11 , 12 ].
Most studies adopted a qualitative approach to data analysis, with Braun & Clarke’s reflexive thematic analysis [ 41 ] being the most prominently used. Story stems were brief to allow participants the freedom to construct their own stories; and story stem design varied widely, with the most common being participants completing a single third-person story stem, with the same story opening provided to all.
Since the COVID-19 pandemic, the pace of research has sped up significantly [ 45 ]. Researchers engaged in population health, health services, or implementation research have worked on ways to accelerate actionable outputs without compromising scientific rigor; for example, rapid qualitative analysis to reduce the time taken to analyze qualitative data [ 46 , 47 ] and methods to hasten on-the-ground implementation [ 48 ]. The story completion method, with its attendant affordances for larger sample sizes, comparative study designs, and streamlined data collection adds to these innovative methods.
There are some limitations to this review. First, we may have missed capturing some studies as the search was restricted to peer-reviewed articles and we did not manually search the reference lists of included papers to identify potential studies for inclusion. Second, we did not include an assessment of the reporting quality of included studies. We attempted to assess the reporting quality of 14 out of 17 included studies which conducted qualitative analysis on collected data, using an established checklist for reporting qualitative research — the Consolidated Criteria for Reporting Qualitative Research, COREQ [ 49 ]. However, many items on the COREQ checklist were neither appropriate nor relevant to the reporting of story completion studies; for example, interview guide, repeat interviews, field notes, participant checking, and so forth. We are mindful of salient scholarly critique regarding COREQ’s trustworthiness and reliability in reflecting the quality of reporting [ 50 ]. Therefore, we could not justifiably adapt COREQ for the purposes of this study.
Strengths of this review include having an extensive search strategy and broad inclusion criteria, allowing us to retrieve as many relevant studies as possible. University librarians were consulted for refinement of search strategy and included studies were not limited to a particular search period or geographical area. We piloted our data extraction form to evaluate its ability to capture relevant study information. Issues were flagged and the form was revised accordingly prior to actual extraction by two researchers.
Currently, there are no universally agreed best practice nor reporting standard for the story completion method in health services research. Given the various ways in which the story completion method has been used in this scoping review, we offer several suggestions for research and practice for further discussions by the scholarly community.
First, piloting is crucial and recommended by key proponents of the story completion method [ 8 , 11 ]. Story completion is a fixed task unlike other qualitative methods such as semi-structured interviews or focus groups where it is possible to iteratively modify the questions as participants co-shape the research-in-progress. Piloting is a smart way to ensure that both the instructions and story stem(s) provided to participants are clear, to prevent misinterpretations.
Second, consider using other quantitative or qualitative research methods to triangulate or corroborate the data from the story completion method if thorough investigation of the research question(s) requires more than one method. While a methodological strength of the story completion method is that it uncovers participants’ patterns and ways of sense-making beyond their lived experiences [ 9 , 14 , 15 , 27 , 35 , 42 ], this also means that there may be limited inferences that can be drawn from the findings since responses may not reflect participants’ realities. Hence, pairing story completion with a story-mediated interview, for example, may lend further insights [ 12 ].
Third, as story completion studies are markedly different from traditional qualitative research methods, having an agreed set of reporting criteria for such studies will be useful for health services researchers. For example, a minimalist set of reporting criteria could comprise the 10-item JBI critical appraisal checklist for qualitative research [ 51 ] plus a description of the study design, development of the story stems, number of participants/sample size, and how participants completed the task in terms of modality, the number of story stems per participant, and sequence of story stem presentation.
The story completion method is an exciting and innovative way of doing qualitative research, and has the potential to be used more widely. This scoping review generated a comprehensive summary of how the story completion method has been used in health-related research. Findings and suggestions for research and practice serve as useful resources for researchers interested in experimenting with and adopting the story completion method in their work.
The dataset supporting the conclusions of this article are available in the Open Science Framework repository, https://osf.io/rk2e6/.
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We thank university librarians from these institutions for consultations on the search strategy: Queensland University of Technology, Australia and Edinburgh Napier University, United Kingdom.
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Candelyn Yu Pong & Elaine Lum
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Author contributions described according to the CRediT taxonomy as follows. Conceptualized the study: EL. Drafted, revised, and finalized the study protocol including search strategy: CYP, EL, and NJR. Conducted the study: CYP and EL. Curated and analyzed the data: CYP and EL. Interpreted the data: EL, CYP, and NJR. Supervised the study: EL. Wrote the first draft of the manuscript including data visualizations: CYP and EL. Revised the manuscript following peer review: EL. Provided critical input to the first draft of the manuscript: NJR. Provided critical input to the revised manuscript: NJR and CYP. All authors approved the final manuscript for submission.
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Pong, C.Y., Roberts, N.J. & Lum, E. The “what, why, and how?” of story completion in health services research: a scoping review. BMC Med Res Methodol 24 , 159 (2024). https://doi.org/10.1186/s12874-024-02274-7
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Endometriosis is one of the most common gynaecological diseases, yet it lacks efficient biomarkers for early detection and unravels disease mechanisms. Proteomic profiling has revealed diverse patterns of protein changes in various clinical samples. Integrating and systematically analysing proteomics data can facilitate the development of biomarkers, expediting diagnosis and providing insights for potential clinical and therapeutic applications. Hence, this systematic review and meta-analysis aimed to explore potential non-invasive diagnostic biomarkers in various biological samples and therapeutic targets for endometriosis.
Online databases, including Scopus, PubMed, Web of Science, MEDLINE, Embase via Ovid, and Google Scholar, were searched using MeSH terms. Two independent authors screened the articles, extracted the data, and assessed the methodological quality of the included studies. GO and KEGG analyses were performed to identify the pathways that were significantly enriched. Protein‑protein interaction and hub gene selection analyses were also conducted to identify biomarker networks for endometriosis.
Twenty-six observational studies with a total of 2,486 participants were included. A total of 644 differentially expressed proteins (180 upregulated and 464 downregulated) were identified from 9 studies. Proteins in peripheral blood exhibited a sensitivity and specificity of 38-100% and 59-99%, respectively, for detecting endometriosis, while proteins in urine had a sensitivity of 58-91% and specificity of 76-93%. Alpha-1-antitrypsin, albumin, and vitamin D binding proteins were significantly DEPs in both serum and urine. Complement C3 is commonly expressed in serum, menstrual blood, and cervical mucus. Additionally, S100-A8 is commonly expressed in both menstrual blood and cervical mucus. Haptoglobin is commonly detected in both serum and plasma, whereas cathepsin G is found in urine, serum, and plasma. GO and KEGG enrichment analyses revealed that proteoglycans in cancer pathways, which regulate cell-to-cell interactions, modulate the extracellular matrix, and promote the proliferation and invasion of endometrial cells, are commonly enriched in serum and urine.
This comprehensive study revealed potential proteomes that were significantly differentially expressed in women with endometriosis utilizing various non-invasive clinical samples. Exploring common differentially expressed proteins in various biological samples provides insights into the diagnosis and pathophysiology of endometriosis, as well as potential clinical and therapeutic applications.
Endometriosis is characterized by the development of endometrium-like tissue and/or stroma outside the endometrium and myometrium [ 1 , 2 ]. It is a chronic inflammatory disease that affects more than 170 million women worldwide, predominantly women of reproductive age, with a wide range of clinical symptoms, including dysmenorrhea, dyspareunia, dyschezia, dysuria, chronic pelvic pain, and infertility, affecting women’s health from the time of menarche to menopause, regardless of their ethnicity or social status [ 1 , 3 ].
In clinical settings, the gold standard diagnostic method for confirming endometriosis is laparoscopy, a minimally invasive surgical procedure that involves inserting an imaging tube through a small incision in the abdomen [ 4 ]. Although laparoscopy is effective and the gold standard, it has potential complications, requires general anaesthesia, and demands advanced surgical skills [ 5 , 6 , 7 ]. Moreover, it is not always available or accessible, particularly in low- and middle-income countries where healthcare facilities and resources are lacking [ 5 ]. Ultrasound is the first-line non-invasive diagnostic method for detecting endometriosis [ 8 ]. It has been widely used to enhance the diagnosis and identification of endometriomas and nodules in adjacent structures of the pelvis but lacks both sensitivity and specificity for ruling out peritoneal endometriosis, endometriosis-associated adhesions, and deep infiltrating endometriosis [ 9 , 10 ]. Imaging techniques such as transvaginal ultrasound (TVS), transrectal ultrasound (TRS), and magnetic resonance imaging (MRI) can bridge the gap between clinical and surgical diagnosis by providing a non-invasive visual diagnosis that can be achieved more quickly, safely, and accessibly than surgery. However, different studies have reported wide variation in diagnostic accuracy between MRI and TVS, mainly due to the variability of techniques, examiners’ experience, and anatomic locations of the lesions/subtypes of the disease [ 11 ]. Given these challenges, non-invasive diagnostic approaches for endometriosis are urgently needed.
While various non-invasive diagnostic modalities involving blood, cervicovaginal fluid, and urine have been proposed, a definitive diagnostic biomarker for endometriosis remains elusive. Despite extensive research into blood and urine tests and the investigation of altered levels of cytokines, angiogenic factors, and growth factors, none of these biomarkers have been used to conclusively diagnose endometriosis [ 12 , 13 , 14 , 15 ]. In addition, numerous studies have demonstrated that nanoparticles, which are materials with dimensions smaller than 100 nanometers, hold promise for improving diagnostic and imaging techniques for non-invasive detection, understanding target signalling pathways, and identifying therapeutic options for diverse diseases [ 16 , 17 , 18 , 19 ]. Notably, nanoparticles can serve as carriers for transporting anti-inflammatory, antioxidant, anti-angiogenic, or immunomodulatory molecules to specific locations [ 20 , 21 , 22 , 23 ], owing to their low toxicity, high stability, and capacity for conjugating with various biomolecules [ 21 , 24 , 25 ]. Moreover, nanotechnology may offer a promising non-invasive diagnostic method for detecting endometriosis by identifying specific biomarkers, such as proteins or genetic materials [ 26 ]. Although studies have shown that CA 19 − 9 and CA-125 have been detected in blood using immunochemical sensing [ 27 , 28 ], the recognition of iron oxide nanoparticles as contrast agents for magnetic resonance imaging [ 26 , 29 ], and the investigation of gold nanorods and carbon nanotubes as photoacoustic imaging agents for visualizing endometriosis lesions in vivo [ 26 , 30 ]. However, it is important to note that none of the biomarkers/methods have been clinically proven biomarkers for endometriosis detection. Among all techniques, proteomic approaches are essential for identifying biomarkers by characterizing the protein content of biological samples [ 31 ]. These approaches enable proteome profiling, comparative expression analysis of proteins in various biological samples, identification of posttranslational modifications, and identification of protein–protein interactions. Notably, proteomic analysis is invaluable because proteins, unlike DNA or RNA, directly mediate cellular functions and disease mechanisms [ 32 , 33 ]. Mass spectrometry (MS) proteomic methods have appeared to be powerful platforms for discovering novel and potential diagnostic and prognostic biomarkers for various diseases. MS-based approaches are substantially helpful for consistently identifying proteins with high diagnostic accuracy for endometriosis [ 34 ]. Furthermore, proteomics studies offer functional insights into expressed proteins and significantly enriched pathways, providing valuable information for understanding the pathogenesis of this disease.
Our hypothesis is that biomarkers of endometriosis commonly found in various biological samples may have substantial significance and have a direct impact on the development and progression of endometriosis. Therefore, our aim is to gain a thorough understanding of the diagnosis, pathogenesis, and possible therapeutic approaches for endometriosis utilizing diverse clinical samples, which could ultimately result in improved patient outcomes and quality of care. Hence, this systematic review aims to assess the utility of proteomic (MS-targeted) analysis for biomarker discovery and navigate the pathogenesis of endometriosis development. Additionally, this study explored the sensitivity and specificity of expressed proteins as promising biomarkers for detecting endometriosis. Moreover, this study involved mass spectrometry-based diagnostic testing for endometriosis and a comprehensive understanding of the pathogenesis of endometriosis in various non-invasive biological samples, including peripheral blood, cervical mucus, menstrual blood, and urine. Remarkably, this study examined commonly enriched pathways associated with disease conditions to better understand the mechanism of disease development.
Following the PRISMA 2020 checklist, we conducted a systematic review and registered the protocol with PROSPERO (registration ID: CRD42023397217).
Searches were performed in the following databases: PubMed, EMBASE through OVID, Google Scholar, Scopus, and Web of Science. The following terms were used in the search strategy, with alternatives as shown using Boolean operators: “mass spectrometry” AND (“diagnostic” OR “test”) AND (“endometriosis” OR “endometrioma”) & (‘’proteomics’’ OR’’ proteome’’ AND (‘’endometriosis’’ OR’’ endometrioma”).
In addition, manual searches were performed for the reference lists of all studies identified by the search strategy described above. Web sources and databases were searched for published articles and preprint research papers written in the English language up to January 31, 2024.
The participants in the study were reproductive-aged women who underwent laparoscopy or abdominal surgery for one of the following reasons: pelvic pain, infertility, dysmenorrhea, abnormal pelvic examination, or a combination of the aforementioned conditions, an ovarian mass regardless of symptoms, or other pelvic pathologies. Only confirmed cases with laparoscopy and/or histology data were included in the review after surgery, while women with confirmed benign pelvic pathologies, such as uterine fibroids, ovarian cysts, unexplained infertility, and fertile healthy women were considered as controls.
From the initial 2,273 retrieved articles, we included 22 case-control, 2 cross-sectional, and 2 prospective cohort studies that met our eligibility criteria. Laparoscopy or laparotomy with or without histological confirmation and mass spectrometry techniques were used as reference standards and index tests, respectively.
In this study, women with a confirmed diagnosis of endometriosis, either combined with one phenotype (I) ovarian endometriosis, (II) deep pelvic infiltrating endometriosis (DIE), and (III) peritoneal endometriosis, were enrolled as cases, whereas women with benign uterine conditions such as uterine fibroids and ovarian cysts and healthy women (self-declaration) were enrolled as controls. All observational studies, such as cohort, cross-sectional, and case-control studies, that were published exclusively in the English language were considered for inclusion.
Endometriosis with other coincidental pelvic pathologies, such as pelvic malignancy, adenomyosis, polycystic ovarian syndrome (PCOS), and pelvic inflammatory disease (PID), studies conducted with approaches other than mass spectrometry-based series, proteomics studies with invasive sources of samples, such as peritoneal fluid, endometrial biopsy, follicular fluid, and endometrial fluid, and studies reporting proteins with other index tests, such as enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR/qPCR), and western blot, were excluded from the study. Additionally, case reports or series, articles without full text and abstracts, duplicated studies, anonymous reports, editorial reports, reviews, perspectives, and book sections or chapters were also excluded.
The authors’ names, year of study, country, diagnostic criteria for endometriosis, type of sample, protein alterations, menstrual phase, proteomics platform, sensitivity, and specificity of biomarkers with a molecular weight of m/z were extracted from each article (Table 1 ). In addition, for the bioinformatics analysis, the protein ID (UniProt), protein accession, and fold change (up- and downregulated) were extracted. Moreover, the protein lists from the 8 articles were extracted, including the identification codes and the level of regulation (up/downregulated). The UniProt website ( https://www.uniprot.org/ ) was used to standardize the protein identification codes. Subsequently, a comparison was conducted on the significantly differentially expressed proteins extracted from the 8 papers to identify consistent proteins. Studies reporting the p value ( p < 0.05) and fold change (FC) of differentially expressed proteins were included in the meta-analysis.
Two authors (GGA & BKA) conducted independent assessments of risks associated with bias and applicability using the Diagnostic Precision Study Quality Assessment Tool (QUADAS-2) for the studies included in the diagnostic accuracy review [ 35 ]. Conflicts between the two authors were evaluated and reviewed by a third author (LW). Patient selection, index test, reference standard, and flow and timing were the four domains used to evaluate the risk of bias, whereas patient selection, index test, and reference standard were the domains employed to assess the applicability of each article. The distribution of risk-of-bias and applicability judgments within each bias domain was assessed (Figure S1 ).
Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to elucidate the biological characteristics of the overlapping DEGs via the online tool database for annotation, visualization, and integrated discovery (DAVID) ( https://david.ncifcrf.gov/ ). GO annotation and KEGG pathway analyses were performed with Metascape ( https://metascape.org/ ). Furthermore, a science and research online plot (SRplot) ( https://www.bioinformatics.com.cn/en ) was used to present the findings. GO and KEGG analyses were performed for each clinical sample separately, such as peripheral blood (serum, plasma), urine, and menstrual blood. DEPs from the supernatant and mesenchymal stem cells derived from menstrual blood were combined and analysed as menstrual blood-expressed proteins. For each given gene list, pathway and process enrichment analyses were carried out with KEGG and GO pathway analyses. Metascape ( https://metascape.org/ ) default parameters: terms with a p value < 0.05, a minimum count of 3, and an enrichment factor > 1.5 were deemed significant. Moreover, p values are calculated based on the cumulative hypergeometric distribution, and q-values are calculated using the Benjamini‒Hochberg procedure to account for multiple tests [ 36 ].
The PPI network was constructed with the STRING ( https://string-db.org/ ) database with a threshold of a combined score > 0.4, and the interaction networks were visualized with Cytoscape (version 3.10.1). In addition, the molecular complex detection (MCODE) plug-in was used to screen strongly interconnected modules in the PPI network with default parameters (degree cut-off = 2, node score cut-off = 0.2, and K-score = 2).
The Cyto-Hubba plug-in in Cytoscape (version 3.10.1) was used to select hub genes in the PPI network. Based on the evidence in the literature, we selected five of the 12 algorithms in the cyto-Hubba plug-in and took the intersection of the five parameters (degree, edge percolated component, maximum neighborhood component, maximal clique centrality, and eccentricity) to determine the hub genes in each biological sample.
A total of 2,273 articles were identified from the online databases with the search strategy. After removing 351 duplicate results, 1922 articles remained. Moreover, 1851 articles were excluded after reviewing the title and abstract, and 71 articles met the eligibility criteria for full-text review and further consideration. Finally, 26 of the 71 identified articles met the eligibility criteria. All selected studies were performed in Asian, American, and European countries (9 in China, 1 in India, 1 in Japan, 3 in the USA, 2 in South Korea, 1 in Belgium, 1 in Germany, 1 in Austria, 2 in Italy, 1 in Australia, 2 in the UK, 1 in Brazil, and 1 in Croatia). Platforms for proteomics included surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF-MS) (8 studies), SOMA scanning (1 study), electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-Q-TOF-MS) (1 study), liquid chromatography‒mass spectrometry (LC‒MS/MS) (9 studies), and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) (7 studies). The biological samples included in this study were peripheral blood (15 studies), urine (8 studies), cervical mucus (1 study), and menstrual blood (2 studies). A PRISMA flow chart that depicts each step is shown in Fig. 1 . The studies analysed in this review were all conducted from 2007 to 2023, and a total of 2,486 women were enrolled.
PRISMA flowchart
Various proteomic techniques have been used to investigate potential biomarkers for detecting endometriosis. Peripheral blood (serum and plasma) protein biomarker analysis has a sensitivity of 38–100% and a specificity of 59–99% for detecting endometriosis (Table 2 ). Additionally, urine proteomic profiling revealed that single and/or combined proteins could detect endometriosis with a sensitivity ranging from 58 to 91% and a specificity ranging from 76 to 93% (Table 2 ).
In endometriosis, different proteins are expressed in various biological samples. Peroxiredoxin-6, angiopoietin-related protein, heterogeneous nuclear ribonucleoproteins, peroxiredoxin-1, leucine-rich alpha-2-glycoprotein, alpha-2-macroglobulin, apolipoprotein L1 and haptoglobin are commonly expressed proteins in plasma and serum samples. Alpha-1-antitrypsin, alpha-enolase, albumin, and vitamin D-binding protein are commonly expressed in both urine and serum, whereas S100-A8 and complement proteins are expressed in cervical mucus and menstrual blood as well as serum. Additionally, dynamin-1-like protein, rho GTPase-activating protein 6, rho GTPase-activating protein 18, zinc finger protein 185, FYN-binding protein 1, rho GTPase-activating protein 45, neurosecretory protein VGF, cartilage oligomeric matrix protein, stromal interaction molecule 1, polymeric immunoglobulin receptor, adipogenesis regulatory factor, complement C3, serum amyloid A-1 protein, fibrinogen gamma chain and ATP-dependent RNA helicase A are differentially expressed proteins in both serum and menstrual blood (Fig. 2 and Table S1 ).
The distribution of DEPs (overexpressed) in endometriosis patients in different clinical samples supplemented with Table S1 : List of differentially expressed proteins
A total of 644 DEPs (180 upregulated and 464 downregulated) were identified from 9 studies in different clinical samples, such as peripheral blood (serum, plasma), menstrual blood, cervical mucus, and urine. Among these studies, 8 met the eligibility requirements for meta-analysis, and the remaining cervical mucus clinical samples were comprehensively reviewed and described (Fig. 3 ).
Top five DEPs in ( a ) plasma, ( b ) serum, ( c ) menstrual blood, and ( d ) urine of women with endometriosis
The DEPs from plasma samples were analysed using GO terms that were categorized into molecular functions, cellular components, and biological processes. The molecular functions of the DEPs were primarily enriched in signalling receptor activator activity, signalling receptor regulator activity, and kinase activity. The GO terms in the cellular component category were mainly related to the collagen-containing extracellular matrix, the external secretory granule lumen, and the extracellular matrix. The biological process GO terms were primarily involved in the regulation of cell activation, regulation of leukocyte activation, and regulation of lymphocyte activation (Fig. 4 & Fig. S6 ). The enriched GO networks are also illustrated in Fig. S2 .
GO and KEGG analyses of the DEPs in women with endometriosis
We conducted KEGG pathway enrichment analysis of DEPs from plasma samples to explore DEP-related gene pathways in endometriosis. Nitrogen metabolism pathways, the phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt) pathway, and microRNAs in cancer pathways were the most significant (Fig. 4 & Fig. S7 ). In general, GO and KEGG analyses revealed that cell proliferation, adhesion, migration, and inflammation are involved in the pathophysiology of endometriosis.
PPI network analysis was performed for the 69 DEPs using the STRING database. After removing proteins without standard symbols, a total of 68 nodes and 121 edges were obtained that represented the interaction network with a p value of 1.98e-10. The top five hub genes identified using the cyto-Hubba plugin included casein kinase II subunit alpha (CSNK2A1, CSNK2A2), mammalian topoisomerase 1 (TOP1), cAMP-dependent protein kinase catalytic subunit alpha (PRKACA) and RNA-binding protein 39 (RBM39) (Fig. 2 ). The MCODE plugin distinguished two cluster networks, and all the top five hub genes, CSNK2A2, CSNK2A1, TOP1, PRKACA and RBM39, were included in the cluster with the highest score.
Category-based GO analysis of the DEPs from serum samples was performed. The cellular component of the DEPs was predominantly enriched in collagen-containing extracellular matrix binding, extracellular matrix, and secretory vesicle lumen. The molecular function category was mainly involved in cell adhesion molecule binding, kinase binding, and actin binding (Fig. 4 & Fig S6 ). Actin filament organization, supramolecular fiber organization, and regulation of body fluid levels are predominantly involved in biological processes. The enriched GO term networks are also illustrated in Fig S3 .
KEGG enrichment pathway analysis was carried out on serum samples to elucidate the pathogenesis of endometriosis. The top ten enriched pathways are illustrated in Fig. 4 and Fig. S7 . The complement and coagulation cascades, platelet activation, neutrophil extracellular trap formation, and tight junction pathways were the most enriched KEGG pathways.
PPI network analysis of the 428 DEPs in serum was performed using the STRING database. A total of 396 nodes and 3186 edges associated with the PPI network were identified after removing proteins with no symbol name (PPI enrichment p value: < 1.0e-16). The five top hub genes were identified using the cytoHubba plugin and included albumin (ALB), actin, cytoplasmic 1 (ACTB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), fibronectin (FN1), and apolipoprotein A-I (APOA1) (Fig. 2 ). The MCODE plugin distinguished two cluster networks, and all the top five hub genes, ALB, ACTB, GAPDH, FN1, and APOA1, were included in the cluster with the highest score.
GO analysis demonstrated that DEPs derived from menstrual blood are involved in the pathophysiology of endometriosis. In addition, the GO analysis results were categorized into three components, i.e., molecular functions, cellular components, and biological processes. The molecular functions of the DEPs were mainly enriched in protease binding, receptor‒ligand activity, and fatty acid binding. The GO terms in the cellular component category were mainly involved in the vesicle lumen, secretory granule lumen and cytoplasmic vesicle lumen (Fig. 4 & Fig. S6 ). Granulocyte migration, granulocyte chemotaxis, and leukocyte chemotaxis are the main biological processes involved. The enriched GO networks are also shown in Fig. S4 .
The enriched KEGG pathways of DEPs from menstrual blood samples were used to further investigate DEP-related gene pathways. The top ten enriched pathways are illustrated in Fig. 4 and Fig. S7 . IL-17 signalling pathway, complement and coagulation cascades, cytokine‒cytokine receptor interaction, and TNF signalling pathway. In conclusion, the GO and KEGG enrichment pathway analyses revealed that angiogenesis, cell proliferation, differentiation, and the induction of inflammation are highly important for the pathogenesis of endometriosis.
The STRING database was used for the PPI network analysis of 110 DEPs. After identifying proteins with no symbol name, there were 89 nodes and 134 edges associated with the PPI network ( p value < 1.0e-16).
The top five hub genes identified using the cyto-Hubba plugin included protein S100 calcium-binding protein A9 (S100-A9), C-X-C motif chemokine ligand 1 (CXCL1), interleukin-1 receptor antagonist protein (IL1RN), cystatin-A (CSTA), and protein S100-A8 (Fig. 2 ). The MCODE plugin illustrated three cluster networks (cluster one: 7 nodes (desmoglein 1 & 3 (DSG1&DSG3), small proline-rich protein 3 (SPRR3), CSTA, small proline-rich protein 1B (SPRR1B), ajuba LIM protein (JUB) and serpin Family B Member 13 (SERPINB13), 19 edges; cluster two: 7 nodes (S100-A8, S100-A9, myeloperoxidase (MPO), IL1RN, C-X-C motif chemokine ligand 1 & 5 (CXCL1, CXCL5); and growth differentiation factor 15 (GDF15), 14 edges; and cluster three: 3 nodes (haptoglobin (HP), cyclic adenosine 3′,5′-monophosphate (CAMP) and resistin (RETN) and 3 edges). The top five hub genes, S100A9, IL1RN, CSTA, S100A8, and CXCL1, were included in the cluster with the highest score.
The three categories of GO term analysis, i.e., molecular functions, cellular components, and biological processes, of the DEPs from urine samples were notably involved in the pathophysiology of endometriosis. The molecular functions of the DEPs were mainly enriched in collagen binding, cytokine binding, and transforming growth factor binding. The GO terms in the cellular components category were mainly involved in the collagen-containing extracellular matrix, secretory vesicle lumen, and extracellular matrix (Fig. 4 & Fig. S6 ). Cell‒cell adhesion, plasminogen activity regulation, and body fluid level regulation are the main biological processes involved. The enriched GO networks are also illustrated in Fig S5 .
The KEGG pathway enrichment of DEPs from urine samples revealed the DEP-related gene pathways that are involved in the mechanism of endometriosis pathogenesis. ECM receptor interactions and microRNAs in cancer pathways were the pathways most significantly associated with endometriosis development (Fig. 4 & Fig. S7 ). Generally, GO and KEGG analyses revealed that cell growth and invasion, adhesion, and angiogenesis were implicated in the pathophysiology of endometriosis.
PPI network analysis of the 22 DEPs was performed using the STRING database, which revealed 22 nodes and 39 edges associated with the PPI network ( p value: 9.7e-14). The top five hub genes identified using the cyto-Hubba plugin included thrombospondin-1 (THBS1), albumin (ALB), CD44 antigen (CD44), annexin A2 (ANXA2), and (LUM) (Fig. 2 ). The MCODE plugin distinguished two cluster networks. In cluster one, CD44, alkaline phosphatase (ALP), zinc-alpha-2-glycoprotein (AZGP1), alpha-1-antitrypsin (SERPINA1), ANAX2, and enolase 1 (ENO1) were the most sub connected proteins, whereas transforming growth factor beta receptor 2 ( TGFBR2), endoglin (ENG), THBS1 and LUM were the most highly connected subnetworks in cluster two.
This is a comprehensive systematic review and meta-analysis of proteomics data to explore common pathways and non-invasive diagnostic biomarkers for detecting endometriosis. Proteomic platforms offer an extraordinary opportunity to overcome the challenges associated with endometriosis by providing valuable insights into the mechanisms underlying the disease and identifying potential markers for diagnosis and therapeutic targeting. Hence, this study focused on recent improvements in proteomics technology aimed at identifying potential non-invasive diagnostic biomarkers and establishing mechanistic pathways to understand the pathogenesis of endometriosis.
This study investigated DEPs in peripheral blood, cervical mucus, menstrual blood, and urine from women with endometriosis. Although many proteins are altered in women with endometriosis, this review illustrates the common DEPs in diverse biological samples from women with endometriosis. DEPs commonly found in multiple biological samples, including vitamin D binding protein (VDBP), haptoglobin, S100-A8, cathepsin G, and complement component 3, are discussed.
VDBP is one of the most common proteins whose expression is altered in women with endometriosis. A line of evidence has shown that the expression of VDBP is substantially increased in the urine [ 37 ] and serum [ 38 ] of women with endometriosis compared to women without endometriosis. Similarly, the expression level of VDBP is markedly higher in endometrial tissue [ 39 ] but lower in peritoneal fluid [ 40 ] in women with endometriosis. Although studies have shown that VDBP may be implicated in the pathogenesis of endometriosis because of its chemotactic characteristics and ability to attract immune cells [ 39 , 40 ], inconsistent patterns of VDBP expression have been observed across studies. The potential reasons for discrepancies may be observed in various studies, attributing them to differences in biological specimens, protein extraction procedures, centrifugal forces, and analysis platforms. Regarding the abundance of VDBP, studies have described diverse techniques for sample handling and analysis, such as 2DE-gel electrophoresis with LC‒MS/MS [ 37 , 38 ] and ELISA [ 41 , 42 ]. These disparities highlight the potential influence of methodological applications, as evidenced by (1) the superior sensitivity of LC‒MS/MS compared to ELISA, (2) the possibility of cell loss in the supernatant, affecting the abundance and concentration of proteins when employing low centrifugation force or short processing time, and (3) the superior sensitivity and ability of ELISA to detect very small amounts of target proteins compared to 2DE-gel electrophoresis [ 43 , 44 ]. These perspectives highlight the clinical utility of LC‒MS/MS, which is a standard and high-throughput proteomics technology with a lesser tendency for bias or interference, as well as greater quantitative agreement among laboratories and biological samples [ 45 , 46 ]. Given the wide range of variation within biological samples that does not adequately explore protein alterations across the severity and phenotype of endometriosis, conducting further large-scale multi-omics studies would be helpful to elucidate the association between VDBP and the underlying mechanism of endometriosis.
The expression level of haptoglobin decreased in the plasma and serum of women with endometriosis [ 47 ]. However, this finding contradicts the findings of Wölfler et al., who demonstrated that the alteration of haptoglobin is significantly increased in the peritoneal fluid of patients with ovarian and peritoneal endometriosis [ 48 ]. The potential variation may be due to the diverse phenotypes of endometriosis, including ovarian, peritoneal, and deep endometriotic lesions, as well as the timing of sample collection. The upregulation of estrogen and the estrogen receptor on macrophages in the peritoneal cavity generates an abnormal immune microenvironment, potentially resulting in increased haptoglobin production [ 49 ]. In addition to the phenotype of endometriosis, the depletion of proteins should also be considered for the variations that ensue. Some studies depleted the most abundant proteins, such as albumin and globulin, to detect low-abundance proteins, which may be putative disease biomarkers in biological samples [ 47 ], whereas other studies did not mention the depletion process during protein extraction and identification [ 50 , 51 , 52 ]. Therefore, protein depletion can affect the haptoglobin concentration during protein extraction via different mechanisms, including reduced solubility, altered protein‒ligand interactions, and competitive binding [ 53 , 54 , 55 ]. The proteomics analysis platform is also another confounding factor. The two common analysis platforms are mass spectrometry and enzyme-linked immunoassay. Both techniques are used to detect the concentration and expression of proteins. However, compared with ELISA, mass spectrometry (MS)-based proteomics analysis [ 47 , 50 ] provides high accuracy, resolution, reproducibility, and sensitivity in identifying and quantifying proteins in a complex mixture, often not allowing differentiation between the peptide and its derivatives or degradation fragments [ 49 , 56 ].
This study similarly demonstrated that the protein S100-A8 is markedly reduced in the cervical mucus of women with endometriosis. This finding supports the findings of a study conducted in France, which identified S100-A8 as a promising endometrial diagnostic marker for both the proliferative and secretory phases [ 57 ]. Additionally, another study showed that S100A8 is predominant in the peritoneal fluid of women with early-stage deep endometriosis [ 51 ]. In addition, the presence of higher levels of S100A8 in the peritoneal fluid of women with endometriosis suggests its potential contribution to the development and formation of lesions within the peritoneal cavity through inflammatory pathways by activating neutrophils [ 58 , 59 ].
This study also revealed that cathepsin G is a common DEP in the urine, serum, and plasma of women with endometriosis. This finding supports the findings of a study conducted in Poland, which revealed that cathepsin G is significantly elevated in the endometrial tissue of women with endometriosis and may play a role in disease development and progression [ 60 ]. Several lines of evidence have demonstrated that cathepsin G plays an essential role in the pathogenesis of endometriosis by promoting extracellular matrix degradation and invasion [ 61 ], activating collagen production [ 61 ], and stimulating the inflammatory process [ 62 ], which facilitates the implantation and growth of endometrial tissue outside the uterus.
This comprehensive study also showed that complement C3 levels are significantly higher in women with endometriosis than in those without endometriosis. Similarly, it has been reported that the abundance of C3 is significantly higher in peritoneal fluid [ 63 ] and endometrial tissue [ 64 , 65 ] in women with endometriosis. The involvement of complement C3, as expressed by ectopic endometrial tissue, in the formation of endometriotic lesions is mediated by mast cell activation. Additionally, it may be generated locally by ectopic endometrial tissue and can promote the engraftment of endometriotic cysts [ 65 , 66 ]. Moreover, cyto-hub gene analysis revealed that CSNK2A1, CSNK2A2, TOP1, PRKACA, RBM39 (plasma), ALB, ACTB, GAPDH, FN1, APOA1 (serum), S100-A9, CXCL1, IL1RN, CSTA, S100-A8 (menstrual blood) and THBS1, ALB, CD44, ANXA2, and LUM (urine) were the top 5 proteins expressed in women with endometriosis. Among all the proteins, ALB is commonly expressed in both serum and urine. These disparities were also revealed by a study conducted by Donal S et al., who reported that the percentages of proteins in venous blood, menstrual blood, and vaginal fluid were 61%, 36%, and 35%, respectively. These body fluid-derived proteins could contribute to augmenting the diagnosis of endometriosis combined with imaging techniques and physical examinations. Nevertheless, to enhance the diagnostic accuracy of non-invasive biological sample-derived proteins, further comprehensive functional and validation multi-omics studies with large sample sizes are needed.
GO analysis revealed that the modulation of molecular, functional, and cellular processes contributes to the pathophysiology of endometriosis through the activation of the collagen-containing extracellular matrix, extracellular matrix, secretory granule lumen, and others [ 67 ]. These GO terms play a role in cell migration, adhesion, angiogenesis, immune response, lymphocyte activation, tissue survival, and facilitating the implantation and potential growth of ectopic endometrial lesions [ 13 , 68 , 69 , 70 , 71 ].
KEGG enrichment analysis revealed that nitrogen metabolism [ 72 ], PI3K-Akt [ 73 ], platelet activation [ 74 ], the NOD-like receptor signalling pathway [ 75 ], ECM-receptor interactions [ 76 ], cytokine‒cytokine receptor interactions [ 76 ], IL-17 signalling [ 77 ], complement and coagulation cascades [ 78 ], TNF signalling and proteoglycans in cancer [ 79 ] have been implicated in the pathogenesis of endometriosis. These pathways play a significant role in the cellular growth and survival of endometriotic lesions [ 80 , 81 , 82 ]. The ECM pathway plays a key role in cell migration, adhesion, and tissue remodelling through the modulation of matrix metalloproteinases that interact with various growth factors and proinflammatory cytokines, such as transforming growth factor-beta (TGF-β), interleukin-1 (IL-1), and tumor necrosis factor-alpha (TNF-α) [ 83 , 84 , 85 ].
The NOD-like receptor pathway is an important signalling pathway that is involved in the pathogenesis of endometriosis [ 86 ]. This pathway encompasses the family pyrin domain containing 3 (NLRP3), an intracellular receptor that initiates the release of proinflammatory cytokines such as interleukin-1β (IL-1β) upon the activation of NLRP3. Abnormal activation of the NLRP3 inflammasome has been observed within ectopic endometrial lesions, peritoneal fluid, and the eutopic endometrium of women with endometriosis. This dysregulated activation significantly contributes to persistent inflammation and accompanying pain related to the condition [ 86 , 87 , 88 , 89 ]. Cytokine‒cytokine receptor interactions and the IL-17 signalling pathway have been implicated in the pathogenesis of endometriosis. IL-17 has been shown to promote the production of other proinflammatory cytokines, such as IL-1α and IL-1β, involved in the pathogenesis of endometriosis [ 77 ]. Additionally, an interaction between the complement system and coagulation system might contribute to the pathophysiology of endometriosis following the monthly shedding of endometrial tissues, triggering complement activation resulting from the activation of the microenvironment in women diagnosed with endometriosis [ 90 ].
Proteoglycans involved in cancer pathways are commonly enriched in both the serum and urine of women with endometriosis. Proteoglycans are complex molecules that are secreted by cancer cells and stromal cells and are composed of glycosaminoglycan (GAG) chains [ 91 ]. The literature has shown that proteoglycans play a significant role in regulating cell-to-cell and cell-to-matrix interactions, releasing growth factors and cytokines that can promote cell proliferation and invasion [ 92 ]. Hence, the trapping and release of angiogenic factors and cytokines that trigger proliferation and invasion are implicated in the pathophysiology of endometriosis.
Overall, this proteomics study provides insights into the expression of common and distinct proteins that are expressed in women with endometriosis. Given the different conditions of the study participants, the phenotype and severity of endometriosis, sample handling, and processing methods, proteomic platforms, and different menstrual cycles, we recommend the use of an integrated multi-OMICS study in which all non-invasive biological samples from the same patients are adjusted for confounders to enhance the mechanism of disease development and provide an opportunity to identify novel diagnostic and therapeutic targets for endometriosis (Fig. 5 ).
Newly proposed approach for the integrative study of endometriosis
This is a comprehensive systematic review and meta-analysis to explore the applicability of the proteomics approach to discover novel diagnostic biomarkers and unravel therapeutic targets from non-invasive biological samples. Additionally, this study serves as an input for further multi-OMICS studies to uncover and establish novel diagnostic and therapeutic targets in endometriosis. There are some limitations in our study. First, there is a lack of sufficient studies on the overall diagnostic accuracy of individual or combined proteins based on the expression molecular weight of proteins/peptides in different phases of the menstrual cycle. Although the literature has shown protein expression in endometriosis during different phases of the human menstrual cycle, the difference in protein expression between the proliferative and secretory phases remains controversial. Therefore, further evidence is required to explore the diagnostic accuracy of protein biomarkers concerning the m/z ratio in different phases of the menstrual cycle. Second, the lack of available raw data and/or full protein lists allowed us to focus only on the differentially expressed protein lists, which could affect the conclusions of the findings. Additionally, the lack of studies did not allow us to look at the differentially expressed proteins across the stages (early vs. advanced, subtypes of endometriosis (ovarian, peritoneal & deep infiltrating) and menstrual cycles (secretary, proliferative and menstrual phases).
In summary, this comprehensive meta-analysis of differentially expressed proteins from non-invasive clinical samples highlights the pathophysiology of endometriosis with GO and enriched KEGG pathways. Moreover, proteomics holds promise for the discovery of peripheral blood, menstrual blood, cervical mucus, and urine-based biomarkers for endometriosis. Various upregulated and downregulated proteins have been identified, suggesting their potential utility as promising non-invasive biomarkers for endometriosis detection and disease development mechanisms.
Furthermore, this review explored how the expression of different proteins and pathways in multiple clinical samples from non-invasive sources can be used to elucidate the pathophysiology of endometriosis. Finally, our findings provide new knowledge that will be helpful in understanding the pathophysiology of endometriosis, and future integrated studies involving peripheral blood, menstrual blood, and urine samples are needed. The identified proteins and pathways not only expand our understanding of the disease but also offer promising targets for future research. Furthermore, validation of these findings, exploration of hub genes for diagnostic accuracy, and further research across a wider range of samples and endometriosis types are key to revealing new options for non-invasive diagnosis and helping to explore more effective potential treatment options. Moreover, further research is needed to validate these findings and potentially help to improve the diagnosis, enhance pathophysiology, and offer hints for potential treatments for endometriosis.
The data underlying this article are available upon the request of the corresponding authors.
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Department of Obstetrics and Gynaecology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR
Getnet Gedefaw Azeze, Ling Wu, Bekalu Kassie Alemu, Wing Fong Lee, Linda Wen Ying Fung, Eva Chun Wai Cheung, Tao Zhang & Chi Chiu Wang
Department of Midwifery, College of Medicine and Health Sciences, Injibara University, Injibara, Ethiopia
Getnet Gedefaw Azeze
Department of Midwifery, College of Medicine and Health Sciences, Debre Markos University, Debre Markos, Ethiopia
Bekalu Kassie Alemu
School of Biomedical Sciences; Li Ka Shing Institute of Health Sciences; Chinese University of Hong Kong – Sichuan University Joint Laboratory in Reproductive Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR
Chi Chiu Wang
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G.G.A. initially began the review and wrote the protocol with help from W.C.C. and Z.T. G.G.A. and B.A.K. performed the data extraction and quality assessment for the selected articles. The analysis was carried out by G.G.A. and W.L. G.G.A. wrote the first draft of the manuscript with the help of W.C.C., Z.T., C.E.C.W., L.W.F., F.L.W.Y. and W.L., who provided feedback on the review and modifications. All authors contributed to and approved the final version of this article.
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: Figure S1. QUADAS-2 tool: The distribution of risk-of-bias (A) and applicability (B) judgments within each bias domain. Figure S2. Network of enriched GO terms in peripheral blood (plasma): (a) biological process, (b) cellular component and (c) molecular function. Figure S3. Network of enriched GO terms in peripheral blood (serum): (a) biological process, (b) cellular component and (c) molecular function. Figure S4. Network of enriched GO terms in menstrual blood. (a) biological process (b) cellular component and (c) molecular function. Figure S5. Network of enriched GO terms in urine: (a) biological process, (b) cellular component and (c) molecular function. Figure S6. GO term analysis of DEPs in plasma, serum, menstrual blood, and urine from patients with endometriosis
: Table S1. List of differentially expressed proteins
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Azeze, G.G., Wu, L., Alemu, B.K. et al. Proteomics approach to discovering non-invasive diagnostic biomarkers and understanding the pathogenesis of endometriosis: a systematic review and meta-analysis. J Transl Med 22 , 685 (2024). https://doi.org/10.1186/s12967-024-05474-3
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This article was co-authored by Jake Adams.Jake Adams is an academic tutor and the owner of Simplifi EDU, a Santa Monica, California based online tutoring business offering learning resources and online tutors for academic subjects K-College, SAT & ACT prep, and college admissions applications.
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