An ecosystem approach to Web3.0: a systematic review and research agenda

Journal of Electronic Business & Digital Economics

ISSN : 2754-4214

Article publication date: 13 July 2023

Issue publication date: 26 July 2023

This paper reviews the extant research on Web3.0 published between 2003 and 2022.


This study uses a topic modeling procedure latent Dirichlet allocation to uncover the research themes and the key phrases associated with each theme.

This study uncovers seven research themes that have been featured in the existing research. In particular, the study highlights the interaction among the research themes that contribute to the understanding of a number of solutions, applications and use cases, such as metaverse and non-fungible tokens.

Research limitations/implications

Despite the relatively small data size of the study, the results remain significant as they contribute to a more profound comprehension of the relevant field and offer guidance for future research directions. The previous analysis revealed that the current Web3.0 technology is still encountering several challenges. Building upon the pioneering research in the field of blockchain, decentralized networks, smart contracts and algorithms, the study proposes an exploratory agenda for future research from an ecosystem approach, targeting to enhance the current state of affairs.


Although topics around Web3.0 have been discussed intensively among the crypto community and technological enthusiasts, there is limited research that provides a comprehensive description of all the related issues and an in-depth analysis of their real-world implications from an ecosystem perspective.

  • Systematic review
  • Decentralized network
  • Smart contract

Guan, C. , Ding, D. , Guo, J. and Teng, Y. (2023), "An ecosystem approach to Web3.0: a systematic review and research agenda", Journal of Electronic Business & Digital Economics , Vol. 2 No. 1, pp. 139-156.

Emerald Publishing Limited

Copyright © 2023, Chong Guan, Ding Ding, Jiancang Guo and Yun Teng

Published in Journal of Electronic Business & Digital Economics . Published by Emerald Publishing Limited. This article is published under the Creative Commons Attribution (CC BY 4.0) licence. Anyone may reproduce, distribute, translate and create derivative works of this article (for both commercial and non-commercial purposes), subject to full attribution to the original publication and authors. The full terms of this licence may be seen at

1. Introduction

Web3.0, also known as Web3, is the next generation of the internet. It incorporates the concepts such as decentralization, blockchain technology and token-based economies ( Bambacht & Pouwelse, 2022 ; Belk, Humayun, & Brouard, 2022 ; Cheng et al. , 2022 ). In April 2014, Gavin Wood first systematically conceptualize Web3.0 as a “decentralized online ecosystem based on blockchain,” which provides developers with the building blocks to create applications in a whole new way ( Wood, 2022 ). Wood argues that in the post-Snowden era, internet users no longer trust enterprises and believe that businesses only manage and use user data for profit. Therefore, there is a need to create internet infrastructure and applications based on the concept of “trustlessness,” meaning that one need not rely on or trust a third party. Web3.0 can be seen as the enforceable Magna Carta of the internet and the cornerstone of individual freedom against authority ( Belk et al. , 2022 ). The concept piqued the interest of venture capital firms, cryptocurrency investors and major technology companies. In particular, starting in late 2021, the number of searches on the internet for the keyword “Web3” grew rapidly (as shown in Figure 1 ). People began to talk enthusiastically about Web3 and companies are starting to prepare for a new business model built on the Web3 platforms.

Web3 is not a new phenomenon but rather a continuation of the cyberpunk and cryptopunk spirit that emerged in the 1980s and 1990s. The current Web3.0 revolution is more like a renaissance after injecting cyberspace with native economic inflows. Cryptocurrencies, non-fungible tokens (NFTs), decentralized autonomous organizations (DAOs), decentralized finance (DeFi) and other concepts are part of the vision for this future blockchain-based web ( Sheridan et al. , 2022 ). The idea that Web3.0, a decentralized, blockchain-based internet ecosystem owned and run by its users, aims to achieve a better and fairer internet, is one of the most persuasive narratives surrounding it ( Bambacht & Pouwelse, 2022 ; Wang et al. , 2022 ). Web3.0 proponents specifically envision an internet where users can reclaim control from a few extractive, centralized institutions and where everyone with an internet connection can compete on equal footing.

Disrupting traditional business models and creating new opportunities: The rise of decentralized applications (DApps) built on blockchain technology is a good example, which has enabled the creation of new marketplaces and platforms for users to exchange value directly with each other without involving centralized authorities.

The creation and use of digital assets and currencies: Web3.0 introduces new types of digital assets and currencies, such as cryptocurrencies and digit tokens. The assets can be used for value transfer, governance, access control and other purposes, and create new economic incentives for users to participate in the ecosystem.

Enabling new forms of peer-to-peer collaboration and value creation: take DAOs as an example, they emerge as a new model for decision-making and resource allocation without involving centralized authorities.

Incubating new business models: Web3.0 is fostering new business models built on decentralized networks and blockchain technology. Companies leveraging the technology can create new products and services and enable users to interact with each other in a decentralized and secure manner.

It is important to note that Web3.0 based on a blockchain decentralized network is distinct from what was described by Tim Berners-Lee’s concept for a Semantic Web ( Berners-Lee, Hendler, & Lassila, 2001 ). The Semantic Web aims to make data machine-readable. Innovative technologies such as resource description framework and web ontology language are the key enablers for encoding semantics with the data ( Blei, 2012 ; Blei, Ng, & Jordan, 2003 ; Mimno, Wallach, Talley, & McCallum, 2011 ). These tools are used to formalize metadata representation. The significant benefits of this integrated semantics include the ability to reason over data and work with a variety of data sources ( Monteiro, 2013 ). However, after a few years of development, the Semantic Web did not materialize in the end due to its technical challenges and other constraints.

Unlike the Semantic Web which focuses on technical advancements, “Web3.0” uses blockchains, cryptocurrencies and NFTs to return ownership and authority to the consumers ( Potts & Rennie, 2019 ). Web3.0 aims to replace the exploitative and unfair web owned and profited by centralized repositories with a decentralized internet where people own their time and data and are fairly reimbursed for it.

Although topics around Web3.0 have been discussed intensively among the crypto community and technological enthusiasts, there is limited research that provides a comprehensive description of all the related issues and an in-depth analysis of their real-world implications. To fill this gap, this study reviews the extant research on Web3.0 published between 2003 and 2022 to obtain a holistic understanding of the current development of Web3.0 and all the related sub-topics. Using a topic modeling procedure, latent Dirichlet allocation (LDA), we uncover seven research themes that have been featured in the existing research and the key phrases associated with each theme. In particular, we highlight the interaction among the research themes that contribute to the understanding of a number of solutions, applications and use cases, such as metaverse and NFT. Building upon the pioneering research in the field of blockchain, decentralized networks, smart contracts and algorithms, we conclude by proposing an exploratory agenda for future research from an ecosystem approach.

2. Evolution of the internet: from Web1.0, Web2.0 to Web3.0

We first review the brief history of the web into two broad periods – Web 1.0 and Web 2.0 – focusing on the key differences between them.

2.1 Web1.0: read-only (1990–2004)

Tim Berners-Lee created the decentralized protocols for the World Wide Web in 1989 at CERN in Geneva, enabling the sharing of knowledge from any location ( Berners-Lee et al. , 2001 ). From 1990 until 2004, the initial development of Web1.0 took place, which primarily consisted of static HTML websites controlled by businesses, and user involvement or interaction was minimal. At this stage, there are few content creators, and most users are simply content consumers. Although there were portals such as America Online and forums such as private chat rooms and bulletin boards (BBs), the internet had little interaction or payment transaction capabilities at the time ( Bevacqua, Carnuccio, Ortale, & Ritacco, 2011 ). Web1.0 was not completely devoid of interaction or payment functions, but these functions were severely limited by the transfer infrastructure’s inability to guarantee security.

2.2 Web2.0: read–write (2004 onwards)

The introduction of social media platforms in 2004 marked the beginning of the Web2.0 era. The web evolved from a read-only medium to a read–write two-way platform. Instead of providing users with materials, businesses began to provide platforms through which users could exchange user-generated content and communicate with one another. As more individuals went online, a small number of leading businesses started to hold a disproportionate percentage of the traffic and value produced on the internet. Web2.0 also created the advertising-based business model ( Monteiro, 2013 ). However, while users may generate content, they did not own it or get paid when it was created. In the Web2.0 era, ordinary web users could exchange information and collaborate on various internet platforms at a very low cost, and the core concept of internet products was interaction, sharing and association ( Bevacqua et al. , 2011 ). The state of the internet service is deteriorating, with users trusting the platforms and giving up their privacy in exchange for better service. At the same time, the platform service providers’ valuation has increased as a result. However, as the business model matures and the platforms’ growth hit a bottleneck, they need to extract more data from users to maintain growth, causing users to lose trust and former partners becoming competitors. Through years of status accumulation, insurmountable entry barriers for new entrepreneurs have been created, impeding the emergence of competition and innovation. This began to erode the interests of various stakeholders and internet users, and the internet is in dire need of a paradigm shift ( Belk et al. , 2022 ).

2.3 Web3.0: read–write–own (2021 onwards)

The decentralization and blockchain technology in Web3.0 provides an improved data ownership and payment model over Web1.0 and 2.0 ( Wang et al. , 2019 ). Centralization, monitoring and exploitative advertising are replaced by transparent and secure decentralized infrastructure and application platforms. In this way, people will be able to legally control their data ( Potts & Rennie, 2019 ). The following are a few fundamental features that serve as its guiding principles:

Decentralized: With Web3.0, ownership is divided among its creators and users rather than being controlled and owned by sizable portions of the internet.

Permissionless: Everyone has equal access to engage in Web3.0 and no one is barred from participating because it is permissionless.

Native payments: Web3.0 replaces banks’ and payment processors’ antiquated infrastructure with cryptocurrency for online purchases and payments.

Trustless: Web3.0 operates without the use of reliable third parties, instead relying on incentives and economic principles.

Interoperability: Web3.0 aims to allow different DApps and platforms to work seamlessly with each other, regardless of the blockchain technology behind them.

Tokenization: Web3.0 enables the creation and management of digital assets which can be used for different purposes.

Users become proprietors in Web3.0’s decentralized network, participating in the development, management and governance of the protocols themselves. Overall, Web3.0 offers improved data ownership, transparency and user control on top of the previous web phases, and the key concepts and elements will be introduced in the following section. The key differences between Web1.0, Web2.0 and Web3.0 are summarized in Table 1 below.

2.4 The core elements of Web3.0

The decentralized technology stack of the Web3.0 model continues to evolve and grow, covering a variety of technologies such as blockchain, smart contracts, prophecy machines, crypto wallets and storage networks. The following section details the key components of the Web3.0 technology stack.

2.4.1 Blockchain

Blockchains are networks with extremely high levels of security and decentralization that allow people to store data, exchange value and record transaction activity in a shared ledger that is not controlled by any centralized entity ( Wang et al. , 2022 ; Yang et al. , 2019 ; Zarrin, Wen Phang, Babu Saheer, & Zarrin, 2021 ). The blockchain network is the backbone of Web3.0, providing a secure execution layer in which cryptographic assets can be created, issued and traded, and programmable smart contracts can be developed. Essentially, the blockchain is the settlement layer of Web3.0, ensuring that all transactions are secure and transparent.

2.4.2 Cryptographic assets

The use of cryptographic assets in Web3.0 is made possible by the secure and decentralized blockchain network, which provides a tamper-proof, environment for transactions ( Belk et al. , 2022 ). Cryptographic assets are the native currency of Web3.0 DApps, which can also be used to pay for Web3.0 services and participate in Web3.0 governance. In Web3.0, a token can represent an investment in a protocol, project or blockchain, and can be used to pay for or secure them. In addition, a token allows the holder to participate in the governance of the protocol or project. For instance, a participant would be able to influence how a network is run or governed if he/she owns a sufficient number of digital tokens for that network. To better understand the concept, potential benefits and applications of token financing models, researchers have extensively studied them ( Chod, Trichakis, & Yang, 2022 ). In addition to token financing, blockchain has also enabled new possibilities in economic activity, such as allowing firms to raise capital via initial coin offerings.

2.4.3 Smart contracts and decentralized applications (DApps)

Smart contracts are computer programs built on blockchain platforms that are tamper-proof and can be executed automatically using code logic that says “if x is true, then execute y.” Programmable smart contracts can create decentralized applications or “DApps,” which are protocols based on the cryptographic economy that laid the groundwork for the development of Web3.0 and put it into the hands of users ( Dannen, 2017 ).

Unlike Web1.0 and Web2.0 applications, DApps are not run by a single entity, but by a decentralized blockchain network. DApps may seem simple, but they are capable of creating very complex automated systems such as peer-to-peer (P2P) financial services in DeFi, data-driven insurance products and play-to-earn (P2E) games.

2.4.4 Prophecy machine

For smart contracts to realize their full potential, they must be able to interact with data and systems outside of the blockchain network. The prophecy machine can connect the blockchain to real-world data and systems and provide the critical infrastructure to create an interoperable and unified Web3.0 ecosystem.

The prophecy machine expands the Web3.0 technology stack to transport off-chain data and services to drive smart contract innovation, enabling cross-chain interoperability to ensure seamless connectivity across blockchains. The prophecy machine infrastructure also provides an entry point for Web2.0 backend systems into the Web3.0 world, enabling legacy systems to easily access any public and private chain seamlessly. Ultimately, the prophecy machine will bring decentralized computing and cryptographic security to legacy systems and build a bridge between Web2.0 and Web3.0 ( Bhutta et al. , 2021 ; Nasir et al. , 2022 ; Renu & Banik, 2021 ).

2.4.5 Identity system

In the Web3.0 model, the front-end of a website or application remains the same, but the backend data structures undergo significant changes. Anyone can participate in verifying transactions and be compensated for their contribution with a network token. From a traditional perspective, Web3.0’s identity system is all about accounts. In professional terms, it is everything that a string of private key hashes can correspond to one by one in a distributed ledger. In a Web3.0 world where accounts (addresses) are generated irreversibly by passwords (private keys), private keys are the lowest level of identity. All of Web3.0’s participants revolve around the private key. In a Web3.0 portal, the identity system is arguably the most important infrastructure besides the blockchain or public chain itself ( Renu & Banik, 2021 ; Shawon, Ahammad, Shetu, Rahman, & Hossain, 2021 ).

3. Web3.0: a systematic review of fundamental approaches and implementations

We operationalized Web3.0 as an umbrella term for online systems that center around decentralization. Because of the exponential growth of blockchain technologies, the chosen scope would be more thoroughly discussed in recent publications. As a result, we focused our research on Web3.0 from 2003 to 2022.

We investigate previous research themes and trending topics in the field of Web3.0 through a comprehensive analysis of the literature. We use an automated technique (web-scraping) to retrieve and compile journal papers, conference proceedings and book chapters from major publisher databases in related fields, such as IEEE, Association for Computing Machinery (ACM), Springer, IGI and Wiley. Considering the rapidly evolving landscape of Web3.0, we have carefully curated papers from repositories of electronic preprints such as arXiv and SSRN. Industry/trade publications, policy briefs and government white papers were excluded to maintain a focus on the scholarly research result. A total of 73 research papers were selected based on the inclusion criteria.

3.1 Topic modeling using latent Dirichlet allocation (LDA)

The abstracts of selected articles were quantitatively analyzed using a probabilistic topic modeling procedure, the LDA approach ( Blei, 2012 ; Blei et al. , 2003 ). This technique can reveal the hidden (latent) structure of the articles determining which articles address similar topics. LDA enables us to determine three components of the hidden structure: (1) a relatively small number of topics as research themes; (2) each article can be considered as a compilation of the topics discovered by the model, with the exact mix determined by how heavily each abstract is weighted toward each topic; (3) Specific words from each featured topic are assigned to the article by the model. This strategy is rooted in the notion that each article is made up of a variety of different topics, each with its own collection of words.

3.2 Results

The optimal number of topics requires quantitative and conceptual evaluation. Topic coherence (C_v), a summary measure that captures “the tendency of a topic’s high probability words to co-occur in the same document,” or simply put, the degree of semantic similarity between top keywords in a topic, is one way to evaluate topic extraction ( Mimno et al. , 2011 ). This metric is based on a sliding window, one-set segmentation of high-scoring words and an indirect confirmation measure that uses a normalized version of the pointwise mutual information criterion and the cosine similarity, which is the metric used in this study to compare model performance.

The coherence score distribution for a variable number of dimensions was sampled to determine the optimal number of dimensions. The coherence scores, C_v, as a function of the number of topics (1 to 10 topics), with α = 0.91 and β = 0.91, are shown in Figure 2 . Seven-topic model was extracted to yield the highest coherence scores, which is chosen for subsequent modeling.

The seven topics shown in Table 2 were identified by the LDA model utilizing their most representative terms and the names we assigned to each of them. These are terms that have a substantially higher chance of occurring in articles concerning that topic than their average chance of appearing across the corpus.

As shown in Table 2 , seven research themes and corresponding keywords have emerged in the area of Web3.0 research throughout the last two decades (2003–2022). We also performed manual content analysis to corroborate the findings with qualitative illustrations of emergent topics. Appendix contains a list of representative text excerpts from the abstracts for each topic, demonstrating how the concepts in the article are related to the Web3.0 ecosystem. The overall findings indicate that research efforts in this field have primarily focused on technology, organizational structure and application practices.

The key research thrusts provide an ecosystem to Web3.0: (1) underlying logic of decentralization, (2) technologies being deployed (e.g., blockchain and smart contracts), (3) governance framework/structure (e.g., peer networks and DAOs), (4) application use cases such as metaverse and (5) targeted outcomes (e.g. user-centric solutions). These prominent research thrusts that have emerged throughout the Web3.0 literature will be discussed in the following section. A conceptual framework that delineated the relationships between the research issues and technical opportunities of Web3.0 is then introduced.

3.3 Discussion

3.3.1 decentralization.

The first stream of research has focused on decentralization, as the key differentiator and defining trait that distinguishes Web3.0 from its previous era ( Liu et al. , 2022 ). This is captured in Topic 6 of our LDA model results. Current research in decentralization is mainly on developing and exploring the application of the decentralized infrastructure. For instance, Bambacht and Pouwelse (2022) conducted the first study on integrating government-issued travel documents into a decentralized societal infrastructure and proved its efficiency, effectiveness and resistance. They highlighted the importance of the decentralized infrastructure for the future of technology and finance. Another study by Panda et al. , in 2021, focused on the consensus algorithms of proof-of-work and proof-of-stake under the concept of decentralization and implemented smart contracts using the Ethereum blockchain platform. Their work was the first step toward the revolution of the current centralized economy to a decentralized one. Decentralization is the backbone of almost all the research studies on Web3.0, and the current exploration in this area is more on the development and application of all the techniques based on the idea of decentralization.

3.3.2 Blockchain technology and interoperable platforms – critical infrastructure enablers for Web3.0

Blockchain technology: Blockchain technology and interoperable platforms provide a digital infrastructure for Web3.0 ( Liu et al. , 2022 ). This stream of research is reflected in Topic 1 under our LDA model results.

By decoupling authentication, organization, computation, communication and mediation from central or intermediary entities, blockchains and interoperable platforms enable decentralized and scalable operations, authentication, communication and collaborations among loosely connected individuals and local nodes to physically, virtually, intellectually or jointly form decentralized ecosystems, resulting in Web3.0 movements. One of the most commonly cited public blockchain platforms is Ethereum, which is also reflected in the keywords in Topic 7 .

Proof-of-work and proof-of-stake: Past research compares and analyses the difference between proof-of-work and proof-of-stake as consensus algorithms that are deployed to govern and regulate blocks on distributed platforms ( Panda & Satapathy, 2021 ). Both methods work toward the same objectives, which are to ensure users are being honest in their transactions and to minimize double spending in the system. Mining is used in proof-of-work to verify bitcoin transactions. According to a set of rules in proof-of-stake, validators are selected based on the “stake” they have in the blockchain, or how much of that token they agree to lock up in order to be considered as a validator. In either scenario, cryptocurrencies are built to be decentralized and distributed, meaning that all computers in the world can see and validate transactions. ( Cao, 2022 ). According to Halaburda, Haeringer, Gans, and Gandal (2022) , the major challenge involved in the process is to handle the absence of trust, as any players can tamper with the blockchain and it would be difficult to identify the “bad” miners.

Interoperation: Blockchains allow assets to be transferred and record transactions through blockchain interoperation. The decentralized identities of individuals, devices and other “things,” with no involvement from centralized entities, are the basic ingredient for blockchain interoperation ( Viriyasitavat, Bi, & Hoonsopon, 2022 ).

Smart contracts: Smart contracts enable digital asset transactions between entities to be conducted on blockchains without human intervention. That is, there is no centralized administrator, server, or trusted authority for authentication, governance, communication, management and mediation in blockchain ecosystems. This stream of research is captured in Topic 5 under our LDA model results.

3.3.3 DAOs – new organizational paradigms to create, engage, govern and implement Web3.0

The Web3.0 protocol enables users to exchange value directly, eliminating the need for trusted service intermediaries ( Potts & Rennie, 2019 ), like Google, Apple or Facebook.

In a massively scaled and interoperable network of decentralized crypto-state, citizens have governance rights. Key research efforts in this field focus on DAOs. DAOs are structured through smart contracts and do not rely on central authorities for governance. Researchers have covered how web3.0 innovation is being organized through DAO frameworks to enable efficient operational and strategic decision-making in the context of distributed information ( Filipčić, 2022 ). Machine-based automation enforces DAO member agreements, in which a set of tamper-resistant rules is predefined and distributed as smart contracts on blockchains. ( Wang et al. , 2019 ). Furthermore, members gain governance rights through tokens issued by DAOs, and on-chain voting is used to arrive at a decentralized consensus on organizational decisions. These outcomes are determined specifically based on the DAO voting mechanisms, which are calculated using tokens via smart contracts ( Zhao, Ai, Lai, Luo, & Benitez, n.d ).

3.3.4 Use cases

Metaverse: The metaverse coined by Neal Stephenson in the 1992 science-fiction novel “Snow Crash” has evolved significantly in terms of vision, conceptualization, execution and applications during the last 30 years. It has progressed from the early stages of the digital twin represented by the online virtual world Second Life to a shared vision among technology entrepreneurs to close the perceived gaps between digital and physical realities with embodied virtual and augmented reality. Technically, the metaverse is thought to broaden the sphere of human action by overcoming natural spatial, time and other resource restrictions ( Cheng et al. , 2022 ).

The metaverse seeks to provide (1) an online or cloud-to-device real-time generated 3D interactive world that provides a comprehensive virtualized or virtually physically integrated immersive experience; (2) human-device interfacing and user-to-user communication and team; and (3) a diverse ecosystem with trading and financial services, economic activities and social interactions ( Cao, 2022 ). Identity management and authentication standards are key to metaverse services.

The metaverse’s virtual economy is backed by the Web3.0 ecosystem, which comprises blockchain technology, smart contracts and NFTs . These decentralized consensus procedures minimize transaction and agency costs and thus enable trustless social and economic interactions.

DApp – Value-based economics'

Another topic that emerge s from our LDA model results is the DApp – Topic 4 . A DApp is a web application with critical components dispersed across a peer-to-peer network ( Zheng, Gao, Huang, & Guan, 2021 ), which is made up of smart contracts that are performed by all nodes on the network at roughly the same time ( Dannen, 2017 ). Past research on DApp deployments encompasses a wide range of solutions: voting ( Pramulia & Anggorojati, 2020 ), crowdfunding ( Dianovics & Majd, 2021 ), tenant management ( Nayak, Narendra, Shukla, & Kempf, 2018 ), ridesharing ( Renu & Banik, 2021 ), certificates verification ( Shawon et al ., 2021 ), among others. In the creative and entertainment industries, one of the experimental use cases of Web3.0 aims to develop artist-centric business solutions, displacing agency-centric business models that facilitate connections between artists and their fans. Blockchain technology enables DApp-based new “value-based economics” in which artists set the terms and conditions of their market involvement through the automation of value components such as payments, licensing and intellectual property (IP) management, contracts, and governance, digital content access and storage ( Potts & Rennie, 2019 ). Such solutions improve supply chain transparency, lower distribution costs and improve the handling of IP and royalties.

3.3.5 User autonomy and user-centricity

Past research has reviewed the challenges faced by the current model of the internet as a result of the influence of centralization. One of the most pressing issues highlighted by ( Zarrin et al. , 2021 ) is trustability. Large Internet firms and service providers can collect, maintain, control, and regulate user data, access and activities. While hosting personalized services and applications in centralized entities can enhance the end-users’ experience, such data monopolies may go beyond monetizing the users’ personal information. Some service providers can use such a centralized model to implement monitoring or censorship, leading to abuse of trust ( Chowdhury, Jahan, Sara, & Nandi, 2020 ). By having users dependent on a centralized service provider, they are exposed to various types of vulnerabilities that could jeopardize the network.

The notion of Web3.0 revolves around user independence and autonomy from centralized services, and the real shift is toward user ownership of digital assets and making people accountable for their data ( Zarrin et al. , 2021 ). Zarrin et al. (2021) examined the potential and capabilities of blockchain-based solutions that can be effectively applied to achieve user autonomy and user-centricity. It can also provide resilience for data protection, offering incentives for users to collaborate ( Yang et al. , 2019 ). DApp reduces the danger of a single point of failure while still ensuring the user experience ( Zheng et al. , 2021 ).

The seven topics generated from LDA have been discussed in detail in the preceding sections. The 73 papers analyzed in this study have been categorized into seven topics based on the keywords summarized from their abstract. The coherence score has been used as an indicator of the model’s performance. Other than the individual topics, the visualizations generated by LDA provide valuable insights into the correlations between different topics and their interrelationships. Topic 1 (blockchain platform) exhibited the highest frequency among all the keywords extracted. Topics 2 to 5 (metaverse, user-centricity, decentralized apps and smart contracts) displayed relatively similar frequencies. Conversely, topics 6 (decentralization) and 7 (transactions) were less common or prominent compared to others. The visualizations not only highlight the relative prevalence of topics but also indicate the interrelationships among them. Notably, topics 3, 5 and 7 were found to be closer, showing a higher degree of similarity and will be discussed together in the following sections, while the rest exhibited greater distinctiveness. The results provided a more comprehensive understanding of the main research topics on Web3.0 and their relationships.

While each of the papers has been assigned to a specific topic, the interlinkage between different topics and the overlapping between the keywords have resulted in many papers describing multiple topics, thus constructing a network of Web3.0 concepts. Figure 3 delineated the relationships between the research issues and technical opportunities of Web3.0 as discussed in the previous section.

By utilizing LDA to analyze pre-sorted literature on Web3.0, the most commonly discussed topics have been identified and the study has provided insights into the current research status in this field. With a better understanding of the current progress and the expected outcomes, potential gaps can be identified and thus prioritized areas for further investigation. The future research direction will be summarized and described in the following section.

4. Toward a research agenda on the ecosystem of Web3.0

As Web3.0 is a relatively new concept that only started to attract attention from researchers in the past decade, the current research on the topics around Web3.0 is still at a very early stage. The LDA analysis provided valuable insights into Web3.0, regarding the main themes and topics that are most frequently studied in the literature. Although we have identified seven distinct themes from the past studies, the width and depth of research coverage in each of the themes vary, and there are still many gaps that need further investigation. In addition, there are also important areas that are not covered by the existing studies but may have significant implications in the future development of Web3.0 and therefore they require more in-depth investigations and urgent attention.

Based on the review and discussion from the previous sections, we identify and propose the following five research areas and relevant issues to be addressed which can serve as a guide for future research agenda.

4.1 The decentralized structure, organization and governance

There has been considerable research and practice development in the area of decentralization; however, research on the organization and governance of decentralized structures is relatively scarce and there remain several issues to be explored further to better understand this new structure of organizations. For instance, in contrast to typical top-down organizations which almost all corporations and nonprofits are, DAOs operate with a flat hierarchical structure, giving all members a voice in important decisions that affect the entire group rather than just the major stakeholders ( Yu, Wang, Bi, Chen, & Xu, 2022 ). While the literature on the DAO has much to offer on the benefit of this entirely new economic organization, there is still work to do on the governance of such new structures, and lessons to be transferred from the DAO literature into other contexts.

4.2 Web3.0 technologies and infrastructure

Blockchain technology and other protocols significantly alter how data are stored, disseminated and retrieved in the decentralized Web3.0 environment while also offering a native transaction layer. Similar to Web2.0 apps, decentralized apps in Web3.0, or “DApps,” are made up of a front-end user interface that communicates with a “smart contract” that is installed on the blockchain. When processing transactions or adding data to the blockchain, the front-end can also communicate with a user’s wallet. The primary distinction between a Web3.0 and a Web2.0 app is that the smart contract and blockchain replace the functions of a standard server and database that are owned and maintained by one person or business.

In 2017, the Web3 Foundation published the 5-level (L0 to L4) Web3.0 Technology Stack ( Figure 4 ). This serves as an important guide to understanding the infrastructure building of Web3.0.

With the technology stack, we can see the important role of blockchain, in particular, the public chain plays in all different layers. The history of the public chain reflects different community groups’ understandings of the world and solutions to the problems. However, like all solutions in the world, old solutions can become new problems. One thing is certain about the future of Web3, the public chain will be the underlying core for a long time, and it will continue to iterate. In terms of blockchain as a whole, public chains are still only MVP (minimum viable product). After we enter the smart contract era started with Ethereum, there are still a lot of “parts” that need to be connected to extend the functionality of public chains to direct applications and make them more accessible to developers, researchers and general users.

Ethereum is the dominant player in the public chain circuit, but its high interaction fees are overwhelming for most users. New public chains with lower transaction fees and faster operation take up the value spillover. With the support of major institutions, developers and users, the new public chain ecosystem has gained tremendous growth in the past year. However, due to technology constraints and competition, most public chains are not directly interoperable with each other, which leaves users, assets, data and DApps sealed off within their ecosystems, creating a silo effect. This is contrary to the spirit of interoperability and scalability of blockchain. The current multi-chain pattern is like a single computer that is not connected to the internet, and there is still a lot of potentials to be released.

Under this circumstance, the cross-chain demand of blockchain natives has started to awaken, and various cross-chain solutions have been launched in the market in time ( Haugum, Hoff, Alsadi, & Li, 2022 ). However, cross-chain technology is still imperfect and security incidents are frequent. This is an area that requires continuous research and investments and may take a long time to bring us to the full development of Web3.0.

4.3 Distributed storage: mechanisms, tracks and issues

As one of the infrastructures of Web3.0, distributed storage is a necessary choice for the decentralization of large-scale on-chain data, especially since it has a unique advantage in solving single points of server failure and data loss. Compared with centralized storage, distributed storage has very competitive advantages in terms of privacy protection, data security and corresponding speed.

At present, the role of distributed storage for the Web3 era has not yet been reflected, and the data stored are mainly reflected in NFT images, on-chain contracts, on-chain graphics and other data with a relatively small memory footprint and low interaction frequency ( Chen et al. , 2022 ). However, the rapid development of the metaverse concept will bring the demand for large-volume data storage such as video, audio and digital model, creating new development opportunities for distributed storage.

Like on-chain finance, distributed storage also faces many practical problems.

First, there is the problem of illegal content regulation. The tamper-evident nature of blockchain also makes the spread of illegal content uncontrollable. Therefore, for distributed storage, how to build a chain-wide regulatory model from the input side to the output side is a problem necessary for it to face mainstream society.

Second, how to improve the storage space utilization of distributed storage. The current distributed data storage has a large portion of junk data and redundancy of stored data. Once it goes to large-scale applications, it remains to be verified whether the current distributed storage projects can quickly adapt to the extremely rapid changes in the market.

4.4 Web3.0 use cases and user experience

In the Web3.0 world, communication and information sharing are being redefined by decentralized technologies. However, the majority of DApps still have user experiences that resemble early web prototypes, and not many of them have a usable front-end. Most people are unaware of the potential of DApps or the blockchain technology that underpins them. The few who have used them have frequently found them challenging and complex. It can be difficult for both developers and designers to communicate the differences between Web2.0 and Web3.0 due to the language, dynamism and visual design of the latter. Solutions need to be user-friendly if the Web3.0 vision is to be widely adopted. Designers may help with this by working closely with engineering teams to make sure these structures are open to and usable by all users.

Currently, a user has several options for interacting with a Smart Contract that has been created on the blockchain: (1) directly through the command line, (2) through the form-like interfaces of their digital wallet or DApp browser or (3) through the richer front-end that the Smart Contract developer already has or will create. The last option, which offers a sophisticated user interface integrated with the experience of working with a blockchain-based distributed application, is undoubtedly the key to the widespread acceptance of DApps.

Currently, the research on Web3.0 user experience mainly focuses on the technical aspects and functionality of DApps, the benefits of the technology and the control of data ownership. However, there is not much discussion on the experiences from the user’s perspective, how users interact with others in the community, and how the user experiences differ from those with Web2.0 applications ( Ali et al. , 2023 ). There is much research that can be done to fill the gap from the perspective of users to help improve the Web3.0 user experience for widespread adoption of Web3.0.

4.5 Regulations and future of Web3.0

With the growing acceptance of crypto tokens globally, there are various financial institutions and services available for the crypto transactions and token economy, providing the financial system necessary for the development of the Web3.0 world.

However, the realities that arise from the virtual finance world, such as the risk of speculation, money laundering and other financial crimes, are receiving increasing attention from regulators in various countries. At the current stage of Web3.0 development, security incidents are frequent and financial losses are huge ( Sheridan et al. , 2022 ).

For instance, in the world of DeFi, most users cannot check the code and rely on the protocol for the security of their funds. If there is a vulnerability in the protocol contract, it may be hacked and cause huge losses. Once the stolen funds enter the coin mixer, the possibility of recovering them is very low. Cross-chain bridges and aggregators are the high-incidence areas. In addition, if the project owner supervises the theft or the private key is lost, it is difficult to check whether it is done intentionally. In the case of anonymous projects, the likelihood of problems occurring is even greater, and it is more difficult to trace the responsibility. This reveals that not only is there a problem with DeFi at the protocol level, but the infrastructure is also not perfect.

At the same time, governments are focusing on promoting innovation and industrial development in the emerging field of Web3, hoping to seize the bonus of the next round of the Internet revolution. How to find a balance between preventing risks and encouraging innovation may be a challenge for regulators in various countries.

In terms of future trends, we need to see the urgent need to promote regulations for cryptocurrency finance to address criminal activity globally. On the other hand, with the revolutionary innovation that cryptocurrency finance and Web3.0 could bring to the economy, it is time to end regulatory fragmentation and act in a unified manner to regulate and promote the development of this sector. The existing regulatory framework was not created with the digital world in mind, and new rules, laws and frameworks must be developed to address it. This is where researchers need to come in and play their role to help us achieve a smooth transition from a Web2.0 world to a Web3.0 world.

In conclusion, this study has highlighted the immense potential of Web3.0 to revolutionize the internet and related applications. Decentralized technologies and the blockchain protocol are the key concepts involved in this new web paradigm. The basic concepts and structures of Web3.0 have been summarized in this study. Topic modeling has been utilized to categorize the filtered corpus into different topics. Seven topics were identified from the results. The topic details have also been discussed. Decentralization serves as the fundamental differentiator of Web3.0 from the current web, with blockchain and smart contracts serving as the underlying technical infrastructure. Metaverse, DApp, and transactions are important components of user-centric use cases within this framework. These topics are interconnected, forming an ecosystem that embodies the essence of Web3.0. Despite the exponential development of the technology, there are still challenges to be addressed and the collaboration of researchers and practitioners in different areas will play a critical role in shaping the Web3.0 landscape and fully utilizing its potential. The new structure still requires further developments, particularly in refining cross-chain technology. Additionally, the data storage needs to adapt to evolving demands, and gaining a deeper understanding of the user perspective is crucial. Lastly, regulations remain a significant challenge that hinders the advancement of Web3.0. Addressing these areas necessitates ongoing effort and input to drive the implementation of this innovative concept. Overall speaking, the literature on Web3.0 provides valuable insights and directions for future research and development.

literature review on web 3 0

Google search trends on “Web3.0” (worldwide)

literature review on web 3 0

Topic coherence: Determining the optimal number of topics

literature review on web 3 0

An ecosystem approach to Web3.0 research topics

literature review on web 3 0

Web3.0 technology stack

Evolution from Web1.0, Web2.0 to Web3.0

Source(s): Appendix by the authors

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English abstract

Purpose – The aim of this paper is to present an integrated literature review exploring the nature of responsive, semantic and interactive Web 3.0 technologies applicable for academic libraries. Design/methodology/approach – We conducted an integrated review of the literature combining a strategy of automated and keywords search. The main source for identifying the studies are Emerald Library Studies and Information & Knowledge Management eJournals, Web of Knowledge, and Library, Information Science & Technology Abstracts (EBSCO) databases. To this end, a sample of (n= 140) studies were analyzed to characterize the Web 3.0 trends and its applications based on theme, years and document types. Findings – A review of literature reveals that Web 3. needs evaluation as to what extent they are integrated, deployed and mainstreamed into library services and in information management practices. It is important to develop a conceptual framework that explores the linkages of Web 3.0 technologies and their applications in academic libraries. Originality/value –This review shows how Web 3.0 technologies enhance library services in its holistic conceptualization and how academic libraries are moving into a more robust, inclusive and adaptable phase in their service values and innovation.

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  • Published: 23 May 2024

Systematic literature review of real-world evidence for treatments in HR+/HER2- second-line LABC/mBC after first-line treatment with CDK4/6i

  • Veronique Lambert   ORCID: 1 ,
  • Sarah Kane   ORCID: 2   na1 ,
  • Belal Howidi   ORCID: 2   na1 ,
  • Bao-Ngoc Nguyen   ORCID: 2   na1 ,
  • David Chandiwana   ORCID: 3 ,
  • Yan Wu   ORCID: 1 ,
  • Michelle Edwards   ORCID: 3 &
  • Imtiaz A. Samjoo   ORCID: 2   na1  

BMC Cancer volume  24 , Article number:  631 ( 2024 ) Cite this article

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Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are currently recommended by the National Comprehensive Cancer Network (NCCN) guidelines and the European Society for Medical Oncology (ESMO) guidelines as the first-line (1 L) treatment for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, locally advanced/metastatic breast cancer (HR+/HER2- LABC/mBC). Although there are many treatment options, there is no clear standard of care for patients following 1 L CDK4/6i. Understanding the real-world effectiveness of subsequent therapies may help to identify an unmet need in this patient population. This systematic literature review qualitatively synthesized effectiveness and safety outcomes for treatments received in the real-world setting after 1 L CDK4/6i therapy in patients with HR+/ HER2- LABC/mBC.

MEDLINE®, Embase, and Cochrane were searched using the Ovid® platform for real-world evidence studies published between 2015 and 2022. Grey literature was searched to identify relevant conference abstracts published from 2019 to 2022. The review was conducted in accordance with PRISMA guidelines (PROSPERO registration: CRD42023383914). Data were qualitatively synthesized and weighted average median real-world progression-free survival (rwPFS) was calculated for NCCN/ESMO-recommended post-1 L CDK4/6i treatment regimens.

Twenty records (9 full-text articles and 11 conference abstracts) encompassing 18 unique studies met the eligibility criteria and reported outcomes for second-line (2 L) treatments after 1 L CDK4/6i; no studies reported disaggregated outcomes in the third-line setting or beyond. Sixteen studies included NCCN/ESMO guideline-recommended treatments with the majority evaluating endocrine-based therapy; five studies on single-agent ET, six studies on mammalian target of rapamycin inhibitors (mTORi) ± ET, and three studies with a mix of ET and/or mTORi. Chemotherapy outcomes were reported in 11 studies. The most assessed outcome was median rwPFS; the weighted average median rwPFS was calculated as 3.9 months (3.3-6.0 months) for single-agent ET, 3.6 months (2.5–4.9 months) for mTORi ± ET, 3.7 months for a mix of ET and/or mTORi (3.0–4.0 months), and 6.1 months (3.7–9.7 months) for chemotherapy. Very few studies reported other effectiveness outcomes and only two studies reported safety outcomes. Most studies had heterogeneity in patient- and disease-related characteristics.


The real-world effectiveness of current 2 L treatments post-1 L CDK4/6i are suboptimal, highlighting an unmet need for this patient population.

Peer Review reports


Breast cancer (BC) is the most diagnosed form of cancer in women with an estimated 2.3 million new cases diagnosed worldwide each year [ 1 ]. BC is the second leading cause of cancer death, accounting for 685,000 deaths worldwide per year [ 2 ]. By 2040, the global burden associated with BC is expected to surpass three million new cases and one million deaths annually (due to population growth and aging) [ 3 ]. Numerous factors contribute to global disparities in BC-related mortality rates, including delayed diagnosis, resulting in a high number of BC cases that have progressed to locally advanced BC (LABC) or metastatic BC (mBC) [ 4 , 5 , 6 ]. In the United States (US), the five-year survival rate for patients who progress to mBC is three times lower (31%) than the overall five-year survival rate for all stages (91%) [ 6 , 7 ].

Hormone receptor (HR) positive (i.e., estrogen receptor and/or progesterone receptor positive) coupled with negative human epidermal growth factor 2 (HER2) expression is the most common subtype of BC, accounting for ∼ 60–70% of all BC cases [ 8 , 9 ]. Historically, endocrine therapy (ET) through estrogen receptor modulation and/or estrogen deprivation has been the standard of care for first-line (1 L) treatment of HR-positive/HER2-negative (HR+/HER2-) mBC [ 10 ]. However, with the approval of the cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) palbociclib in combination with the aromatase inhibitor (AI) letrozole in 2015 by the US Food and Drug Administration (FDA), 1 L treatment practice patterns have evolved such that CDK4/6i (either in combination with AIs or with fulvestrant) are currently considered the standard of care [ 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. Other CDK4/6i (ribociclib and abemaciclib) in combination with ET are approved for the treatment of HR+/HER2- LABC/mBC; 1 L use of ribociclib in combination with an AI was granted FDA approval in March 2017 for postmenopausal women (with expanded approval in July 2018 for pre/perimenopausal women and for use in 1 L with fulvestrant for patients with disease progression on ET as well as for postmenopausal women), and abemaciclib in combination with fulvestrant was granted FDA approval in September 2017 for patients with disease progression following ET and as monotherapy in cases where disease progression occurs following ET and prior chemotherapy in mBC (with expanded approval in February 2018 for use in 1 L in combination with an AI for postmenopausal women) [ 18 , 19 , 20 , 21 ].

Clinical trials investigating the addition of CDK4/6i to ET have demonstrated significant improvement in progression-free survival (PFS) and significant (ribociclib) or numerical (palbociclib and abemaciclib) improvement in overall survival (OS) compared to ET alone in patients with HR+/HER2- advanced or mBC, making this combination treatment the recommended option in the 1 L setting [ 22 , 23 , 24 , 25 , 26 , 27 ]. However, disease progression occurs in a significant portion of patients after 1 L CDK4/6i treatment [ 28 ] and the optimal treatment sequence after progression on CDK4/6i remains unclear [ 29 ]. At the time of this review (literature search conducted December 14, 2022), guidelines by the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO) recommend various options for the treatment of HR+/HER2- advanced BC in the second-line (2 L) setting, including fulvestrant monotherapy, mammalian target of rapamycin inhibitors (mTORi; e.g., everolimus) ± ET, alpelisib + fulvestrant (if phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha mutation positive [PIK3CA-m+]), poly-ADP ribose polymerase inhibitors (PARPi) including olaparib or talazoparib (if breast cancer gene/partner and localizer of BRCA2 positive [BRCA/PALB2m+]), and chemotherapy (in cases when a visceral crisis is present) [ 15 , 16 ]. CDK4/6i can also be used in 2 L [ 16 , 30 ]; however, limited data are available to support CDK4/6i rechallenge after its use in the 1 L setting [ 15 ]. Depending on treatments used in the 1 L and 2 L settings, treatment in the third-line setting is individualized based on the patient’s response to prior treatments, tumor load, duration of response, and patient preference [ 9 , 15 ]. Understanding subsequent treatments after 1 L CDK4/6i, and their associated effectiveness, is an important focus in BC research.

Treatment options for HR+/HER2- LABC/mBC continue to evolve, with ongoing research in both clinical trials and in the real-world setting. Real-world evidence (RWE) offers important insights into novel therapeutic regimens and the effectiveness of treatments for HR+/HER2- LABC/mBC. The effectiveness of the current treatment options following 1 L CDK4/6i therapy in the real-world setting highlights the unmet need in this patient population and may help to drive further research and drug development. In this study, we conducted a systematic literature review (SLR) to qualitatively summarize the effectiveness and safety of treatment regimens in the real-world setting after 1 L treatment with CDK4/6i in patients with HR+/HER2- LABC/mBC.

Literature search

An SLR was performed in accordance with the Cochrane Handbook for Systematic Reviews of Interventions [ 31 ] and reported in alignment with the Preferred Reporting Items for Systematic Literature Reviews and Meta-Analyses (PRISMA) statement [ 32 ] to identify all RWE studies assessing the effectiveness and safety of treatments used for patients with HR+/HER2- LABC/mBC following 1 L CDK4/6i therapy and received subsequent treatment in 2 L and beyond (2 L+). The Ovid® platform was used to search MEDLINE® (including Epub Ahead of Print and In-Process, In-Data-Review & Other Non-Indexed Citations), Ovid MEDLINE® Daily, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews by an experienced medical information specialist. The MEDLINE® search strategy was peer-reviewed independently by a senior medical information specialist before execution using the Peer Review of Electronic Search Strategies (PRESS) checklist [ 33 ]. Searches were conducted on December 14, 2022. The review protocol was developed a priori and registered with the International Prospective Register of Systematic Review (PROSPERO; CRD42023383914) which outlined the population, intervention, comparator, outcome, and study design (PICOS) criteria and methodology used to conduct the review (Table  1 ).

Search strategies utilized a combination of controlled vocabulary (e.g., “HER2 Breast Cancer” or “HR Breast Cancer”) and keywords (e.g., “Retrospective studies”). Vocabulary and syntax were adjusted across databases. Published and validated filters were used to select for study design and were supplemented using additional medical subject headings (MeSH) terms and keywords to select for RWE and nonrandomized studies [ 34 ]. No language restrictions were included in the search strategy. Animal-only and opinion pieces were removed from the results. The search was limited to studies published between January 2015 and December 2022 to reflect the time at which FDA approval was granted for the first CDK4/6i agent (palbociclib) in combination with AI for the treatment of LABC/mBC [ 35 ]. Further search details are presented in Supplementary Material 1 .

Grey literature sources were also searched to identify relevant abstracts and posters published from January 2019 to December 2022 for prespecified relevant conferences including ESMO, San Antonio Breast Cancer Symposium (SABCS), American Society of Clinical Oncology (ASCO), the International Society for Pharmacoeconomics and Outcomes Research (ISPOR US), and the American Association for Cancer Research (AACR). A search of was conducted to validate the findings from the database and grey literature searches.

Study selection, data extraction & weighted average calculation

Studies were screened for inclusion using DistillerSR Version 2.35 and 2.41 (DistillerSR Inc. 2021, Ottawa, Canada) by two independent reviewers based on the prespecified PICOS criteria (Table  1 ). A third reviewer was consulted to resolve any discrepancies during the screening process. Studies were included if they reported RWE on patients aged ≥ 18 years with HR+/HER2- LABC/mBC who received 1 L CDK4/6i treatment and received subsequent treatment in 2 L+. Studies were excluded if they reported the results of clinical trials (i.e., non-RWE), were published in any language other than English, and/or were published prior to 2015 (or prior to 2019 for conference abstracts and posters). For studies that met the eligibility criteria, data relating to study design and methodology, details of interventions, patient eligibility criteria and baseline characteristics, and outcome measures such as efficacy, safety, tolerability, and patient-reported outcomes (PROs), were extracted (as available) using a Microsoft Excel®-based data extraction form (Microsoft Corporation, WA, USA). Data extraction was performed by a single reviewer and was confirmed by a second reviewer. Multiple publications identified for the same RWE study, patient population, and setting that reported data for the same intervention were linked and extracted as a single publication. Weighted average median real-world progression-free survival (rwPFS) values were calculated by considering the contribution to the median rwPFS of each study proportional to its respective sample size. These weighted values were then used to compute the overall median rwPFS estimate.

Quality assessment

The Newcastle-Ottawa scale (NOS) for nonrandomized (cohort) studies was used to assess the risk of bias for published, full-text studies [ 36 ]. The NOS allocates a maximum of nine points for the least risk of bias across three domains: (1) Formation of study groups (four points), (2) Comparability between study groups (two points), (3) Outcome ascertainment (three points). NOS scores can be categorized in three groups: very high risk of bias (0 to 3 points), high risk of bias (4 to 6), and low risk of bias (7 to 9) [ 37 ]. Risk of bias assessment was performed by one reviewer and validated by a second independent reviewer to verify accuracy. Due to limited methodological data by which to assess study quality, risk of bias assessment was not performed on conference abstracts or posters. An amendment to the PROSPERO record (CRD42023383914) for this study was submitted in relation to the quality assessment method (specifying usage of the NOS).

The database search identified 3,377 records; after removal of duplicates, 2,759 were screened at the title and abstract stage of which 2,553 were excluded. Out of the 206 reports retrieved and assessed for eligibility, an additional 187 records were excluded after full-text review; most of these studies were excluded for having patients with mixed lines of CDK4/6i treatment (i.e., did not receive CDK4/6i exclusively in 1 L) (Fig.  1 and Table S1 ). The grey literature search identified 753 records which were assessed for eligibility; of which 752 were excluded mainly due to the population not meeting the eligibility criteria (Fig.  1 ). In total, the literature searches identified 20 records (9 published full-text articles and 11 conference abstracts/posters) representing 18 unique RWE studies that met the inclusion criteria. The NOS quality scores for the included full-text articles are provided in Table S2 . The scores ranged from four to six points (out of a total score of nine) and the median score was five, indicating that all the studies suffered from a high risk of bias [ 37 ].

Most studies were retrospective analyses of chart reviews or medical registries, and all studies were published between 2017 and 2022 (Table S3 ). Nearly half of the RWE studies (8 out of 18 studies) were conducted in the US [ 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ], while the remaining studies included sites in Canada, China, Germany, Italy, Japan, and the United Kingdom [ 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ]. Sample sizes ranged from as few as 4 to as many as 839 patients across included studies, with patient age ranging from 26 to 86 years old.

Although treatment characteristics in the 1 L setting were not the focus of the present review, these details are captured in Table S3 . Briefly, several RWE studies reported 1 L CDK4/6i use in combination with ET (8 out of 18 studies) or as monotherapy (2 out of 18 studies) (Table S3 ). Treatments used in combination with 1 L CDK4/6i included letrozole, fulvestrant, exemestane, and anastrozole. Where reported (4 out of 18 studies), palbociclib was the most common 1 L CDK4/6i treatment. Many studies (8 out of 18 studies) did not report which specific CDK4/6i treatment(s) were used in 1 L or if its administration was in combination or monotherapy.

Characteristics of treatments after 1 L CDK4/6i therapy

Across all studies included in this review, effectiveness and safety data were only available for treatments administered in the 2 L setting after 1 L CDK4/6i treatment. No studies were identified that reported outcomes for patients treated in the third-line setting or beyond after 1 L CDK4/6i treatment. All 18 studies reported effectiveness outcomes in 2 L, with only two of these studies also describing 2 L safety outcomes. The distribution of outcomes reported in these studies is provided in Table S4 . Studies varied in their reporting of outcomes for 2 L treatments; some studies reported outcomes for a group of 2 L treatments while others described independent outcomes for specific 2 L treatments (i.e., everolimus, fulvestrant, or chemotherapy agents such as eribulin mesylate) [ 42 , 45 , 50 , 54 , 55 ]. Due to the heterogeneity in treatment classes reported in these studies, this data was categorized (as described below) to align with the guidelines provided by NCCN and ESMO [ 15 , 16 ]. The treatment class categorizations for the purpose of this review are: single-agent ET (patients who exclusively received a single-agent ET after 1 L CDK4/6i treatment), mTORi ± ET (patients who exclusively received an mTORi with or without ET after 1 L CDK4/6i treatment), mix of ET and/or mTORi (patients who may have received only ET, only mTORi, and/or both treatments but the studies in this group lacked sufficient information to categorize these patients in the “single-agent ET” or “mTOR ± ET” categories), and chemotherapy (patients who exclusively received chemotherapy after 1 L CDK4/6i treatment). Despite ESMO and NCCN guidelines indicating that limited evidence exists to support rechallenge with CDK4/6i after 1 L CDK4/6i treatment [ 15 , 16 ], two studies reported outcomes for this treatment approach. Data for such patients were categorized as “ CDK4/6i ± ET ” as it was unclear how many patients receiving CDK4/6i rechallenge received concurrent ET. All other patient groups that lacked sufficient information or did not report outcome/safety data independently (i.e., grouped patients with mixed treatments) to categorize as one of the treatment classes described above were grouped as “ other ”.

The majority of studies reported effectiveness outcomes for endocrine-based therapy after 1 L CDK4/6i treatment; five studies for single-agent ET, six studies for mTORi ± ET, and three studies for a mix of ET and/or mTORi (Fig.  2 ). Eleven studies reported effectiveness outcomes for chemotherapy after 1 L CDK4/6i treatment, and only two studies reported effectiveness outcomes for CDK4/6i rechallenge ± ET. Eight studies that described effectiveness outcomes were grouped into the “other” category. Safety data was only reported in two studies: one study evaluating the chemotherapy agent eribulin mesylate and one evaluating the mTORi everolimus.

Effectiveness outcomes

Real-world progression-free survival

Median rwPFS was described in 13 studies (Tables  2 and Table S5 ). Across the 13 studies, the median rwPFS ranged from 2.5 months [ 49 ] to 17.3 months [ 39 ]. Out of the 13 studies reporting median rwPFS, 10 studies reported median rwPFS for a 2 L treatment recommended by ESMO and NCCN guidelines, which ranged from 2.5 months [ 49 ] to 9.7 months [ 45 ].

Weighted average median rwPFS was calculated for 2 L treatments recommended by both ESMO and NCCN guidelines (Fig.  3 ). The weighted average median rwPFS for single-agent ET was 3.9 months ( n  = 92 total patients) and was derived using data from two studies reporting median rwPFS values of 3.3 months ( n  = 70) [ 38 ] and 6.0 months ( n  = 22) [ 40 ]. For one study ( n  = 7) that reported outcomes for single agent ET, median rwPFS was not reached during the follow-up period; as such, this study was excluded from the weighted average median rwPFS calculation [ 49 ].

The weighted average median rwPFS for mTORi ± ET was 3.6 months ( n  = 128 total patients) and was derived based on data from 3 studies with median rwPFS ranging from 2.5 months ( n  = 4) [ 49 ] to 4.9 months ( n  = 25) [ 54 ] (Fig.  3 ). For patients who received a mix of ET and/or mTORi but could not be classified into the single-agent ET or mTORi ± ET treatment classes, the weighted average median rwPFS was calculated to be 3.7 months ( n  = 17 total patients). This was calculated based on data from two studies reporting median rwPFS values of 3.0 months ( n  = 5) [ 46 ] and 4.0 months ( n  = 12) [ 49 ]. Notably, one study of patients receiving ET and/or everolimus reported a median rwPFS duration of 3.0 months; however, this study was excluded from the weighted average median rwPFS calculation for the ET and/or mTORi class as the sample size was not reported [ 53 ].

The weighted average median rwPFS for chemotherapy was 6.1 months ( n  = 499 total patients), calculated using data from 7 studies reporting median rwPFS values ranging from 3.7 months ( n  = 249) [ 38 ] to 9.7 months ( n  = 121) [ 45 ] (Fig.  3 ). One study with a median rwPFS duration of 5.6 months was not included in the weighted average median rwPFS calculation as the study did not report the sample size [ 53 ]. A second study was excluded from the calculation since the reported median rwPFS was not reached during the study period ( n  = 7) [ 41 ].

Although 2 L CDK4/6i ± ET rechallenge lacks sufficient information to support recommendation by ESMO and NCCN guidelines, the limited data currently available for this treatment have shown promising results. Briefly, two studies reported median rwPFS for CDK4/6i ± ET with values of 8.3 months ( n  = 302) [ 38 ] and 17.3 months ( n  = 165) (Table  2 ) [ 39 ]. The remaining median rwPFS studies reported data for patients classified as “Other” (Table S5 ). The “Other” category included median rwPFS outcomes from seven studies, and included a myriad of treatments (e.g., ET, mTOR + ET, chemotherapy, CDK4/6i + ET, alpelisib + fulvestrant, chidamide + ET) for which disaggregated median rwPFS values were not reported.

Overall survival

Median OS for 2 L treatment was reported in only three studies (Table  2 ) [ 38 , 42 , 43 ]. Across the three studies, the 2 L median OS ranged from 5.2 months ( n  = 3) [ 43 ] to 35.7 months ( n  = 302) [ 38 ]. Due to the lack of OS data in most of the studies, weighted averages could not be calculated. No median OS data was reported for the single-agent ET treatment class whereas two studies reported median OS for the mTORi ± ET treatment class, ranging from 5.2 months ( n  = 3) [ 43 ] to 21.8 months ( n  = 54) [ 42 ]. One study reported 2 L median OS of 24.8 months for a single patient treated with chemotherapy [ 43 ]. The median OS data in the CDK4/6i ± ET rechallenge group was 35.7 months ( n  = 302) [ 38 ].

Patient mortality was reported in three studies [ 43 , 44 , 45 ]. No studies reported mortality for the single-agent ET treatment class and only one study reported this outcome for the mTORi ± ET treatment class, where 100% of patients died ( n  = 3) as a result of rapid disease progression [ 43 ]. For the chemotherapy class, one study reported mortality for one patient receiving 2 L capecitabine [ 43 ]. An additional study reported eight deaths (21.7%) following 1 L CDK4/6i treatment; however, this study did not disclose the 2 L treatments administered to these patients [ 44 ].

Other clinical endpoints

The studies included limited information on additional clinical endpoints; two studies reported on time-to-discontinuation (TTD), two reported on duration of response (DOR), and one each on time-to-next-treatment (TTNT), time-to-progression (TTP), objective response rate (ORR), clinical benefit rate (CBR), and stable disease (Tables  2 and Table S5 ).

Safety, tolerability, and patient-reported outcomes

Safety and tolerability data were reported in two studies [ 40 , 45 ]. One study investigating 2 L administration of the chemotherapy agent eribulin mesylate reported 27 patients (22.3%) with neutropenia, 3 patients (2.5%) with febrile neutropenia, 10 patients (8.3%) with peripheral neuropathy, and 14 patients (11.6%) with diarrhea [ 45 ]. Of these, neutropenia of grade 3–4 severity occurred in 9 patients (33.3%) [ 45 ]. A total of 55 patients (45.5%) discontinued eribulin mesylate treatment; 1 patient (0.83%) discontinued treatment due to adverse events [ 45 ]. Another study reported that 5 out of the 22 patients receiving the mTORi everolimus combined with ET in 2 L (22.7%) discontinued treatment due to toxicity [ 40 ]. PROs were not reported in any of the studies included in the SLR.

The objective of this study was to summarize the existing RWE on the effectiveness and safety of therapies for patients with HR+/HER2- LABC/mBC after 1 L CDK4/6i treatment. We identified 18 unique studies reporting specifically on 2 L treatment regimens after 1 L CDK4/6i treatment. The weighted average median rwPFS for NCCN- and ESMO- guideline recommended 2 L treatments ranged from 3.6 to 3.9 months for ET-based treatments and was 6.1 months when including chemotherapy-based regimens. Treatment selection following 1 L CDK4/6i therapy remains challenging primarily due to the suboptimal effectiveness or significant toxicities (e.g., chemotherapy) associated with currently available options [ 56 ]. These results highlight that currently available 2 L treatments for patients with HR+/HER2- LABC/mBC who have received 1 L CDK4/6i are suboptimal, as evidenced by the brief median rwPFS duration associated with ET-based treatments, or notable side effects and toxicity linked to chemotherapy. This conclusion is aligned with a recent review highlighting the limited effectiveness of treatment options for HR+/HER2- LABC/mBC patients post-CDK4/6i treatment [ 56 , 57 ]. Registrational trials which have also shed light on the short median PFS of 2–3 months achieved by ET (i.e., fulvestrant) after 1 L CDK4/6i therapy emphasize the need to develop improved treatment strategies aimed at prolonging the duration of effective ET-based treatment [ 56 ].

The results of this review reveal a paucity of additional real-world effectiveness and safety evidence after 1 L CDK4/6i treatment in HR+/HER2- LABC/mBC. OS and DOR were only reported in two studies while other clinical endpoints (i.e., TTD, TTNT, TTP, ORR, CBR, and stable disease) were only reported in one study each. Similarly, safety and tolerability data were only reported in two studies each, and PROs were not reported in any study. This hindered our ability to provide a comprehensive assessment of real-world treatment effectiveness and safety following 1 L CDK4/6i treatment. The limited evidence may be due to the relatively short period of time that has elapsed since CDK4/6i first received US FDA approval for 1 L treatment of HR+/HER2- LABC/mBC (2015) [ 35 ]. As such, almost half of our evidence was informed by conference abstracts. Similarly, no real-world studies were identified in our review that reported outcomes for treatments in the third- or later-lines of therapy after 1 L CDK4/6i treatment. The lack of data in this patient population highlights a significant gap which limits our understanding of the effectiveness and safety for patients receiving later lines of therapy. As more patients receive CDK4/6i therapy in the 1 L setting, the number of patients requiring subsequent lines of therapy will continue to grow. Addressing this data gap over time will be critical to improve outcomes for patients with HR+/HER2- LABC/mBC following 1 L CDK4/6i therapy.

There are several strengths of this study, including adherence to the guidelines outlined in the Cochrane Handbook to ensure a standardized and reliable approach to the SLR [ 58 ] and reporting of the SLR following PRISMA guidelines to ensure transparency and reproducibility [ 59 ]. Furthermore, the inclusion of only RWE studies allowed us to assess the effectiveness of current standard of care treatments outside of a controlled environment and enabled us to identify an unmet need in this patient population.

This study had some notable limitations, including the lack of safety and additional effectiveness outcomes reported. In addition, the dearth of studies reporting PROs is a limitation, as PROs provide valuable insight into the patient experience and are an important aspect of assessing the impact of 2 L treatments on patients’ quality of life. The studies included in this review also lacked consistent reporting of clinical characteristics (e.g., menopausal status, sites of metastasis, prior surgery) making it challenging to draw comprehensive conclusions or comparisons based on these factors across the studies. Taken together, there exists an important gap in our understanding of the long-term management of patients with HR+/HER2- LABC/mBC. Additionally, the effectiveness results reported in our evidence base were informed by small sample sizes; many of the included studies reported median rwPFS based on less than 30 patients [ 39 , 40 , 41 , 46 , 49 , 51 , 60 ], with two studies not reporting the sample size at all [ 47 , 53 ]. This may impact the generalizability and robustness of the results. Relatedly, the SLR database search was conducted in December 2022; as such, novel agents (e.g., elacestrant and capivasertib + fulvestrant) that have since received FDA approval for the treatment of HR+/HER2- LABC/mBC may impact current 2 L rwPFS outcomes [ 61 , 62 ]. Finally, relative to the number of peer-reviewed full-text articles, this SLR identified eight abstracts and one poster presentation, comprising half (50%) of the included unique studies. As conference abstracts are inherently limited by how much content that can be described due to word limit constraints, this likely had implications on the present synthesis whereby we identified a dearth of real-world effectiveness outcomes in patients with HR+/HER2- LABC/mBC treated with 1 L CDK4/6i therapy.

Future research in this area should aim to address the limitations of the current literature and provide a more comprehensive understanding of optimal sequencing of effective and safe treatment for patients following 1 L CDK4/6i therapy. Specifically, future studies should strive to report robust data related to effectiveness, safety, and PROs for patients receiving 2 L treatment after 1 L CDK4/6i therapy. Future studies should also aim to understand the mechanism underlying CDK4/6i resistance. Addressing these gaps in knowledge may improve the long-term real-world management of patients with HR+/HER2- LABC/mBC. A future update of this synthesis may serve to capture a wider breadth of full-text, peer-reviewed articles to gain a more robust understanding of the safety, effectiveness, and real-world treatment patterns for patients with HR+/HER2- LABC/mBC. This SLR underscores the necessity for ongoing investigation and the development of innovative therapeutic approaches to address these gaps and improve patient outcomes.

This SLR qualitatively summarized the existing real-world effectiveness data for patients with HR+/HER2- LABC/mBC after 1 L CDK4/6i treatment. Results of this study highlight the limited available data and the suboptimal effectiveness of treatments employed in the 2 L setting and underscore the unmet need in this patient population. Additional studies reporting effectiveness and safety outcomes, in addition to PROs, for this patient population are necessary and should be the focus of future research.

figure 1

PRISMA flow diagram. *Two included conference abstracts reported the same information as already included full-text reports, hence both conference abstracts were not identified as unique. Abbreviations: 1 L = first-line; AACR = American Association of Cancer Research; ASCO = American Society of Clinical Oncology; CDK4/6i = cyclin-dependent kinase 4/6 inhibitor; ESMO = European Society for Medical Oncology; ISPOR = Professional Society for Health Economics and Outcomes Research; n = number of studies; NMA = network meta-analysis; pts = participants; SABCS = San Antonio Breast Cancer Symposium; SLR = systematic literature review.

figure 2

Number of studies reporting effectiveness outcomes exclusively for each treatment class. *Studies that lack sufficient information on effectiveness outcomes to classify based on the treatment classes outlined in the legend above. Abbreviations: CDK4/6i = cyclin-dependent kinase 4/6 inhibitor; ET = endocrine therapy; mTORi = mammalian target of rapamycin inhibitor.

figure 3

Weighted average median rwPFS for 2 L treatments (recommended in ESMO/NCCN guidelines) after 1 L CDK4/6i treatment. Circular dot represents weighted average median across studies. Horizontal bars represent the range of values reported in these studies. Abbreviations: CDK4/6i = cyclin-dependent kinase 4/6 inhibitor; ESMO = European Society for Medical Oncology; ET = endocrine therapy, mTORi = mammalian target of rapamycin inhibitor; n = number of patients; NCCN = National Comprehensive Cancer Network; rwPFS = real-world progression-free survival.

Data availability

All data generated or analyzed during this study are included in this published article [and its supplementary information files]. This study is registered with PROSPERO (CRD42023383914).



Second-line treatment setting and beyond

American Association of Cancer Research

Aromatase inhibitor

American Society of Clinical Oncology

  • Breast cancer

breast cancer gene/partner and localizer of BRCA2 positive

Clinical benefit rate

Cyclin-dependent kinase 4/6 inhibitor

Complete response

Duration of response

European Society for Medical Oncology

Food and Drug Administration

Human epidermal growth factor receptor 2

Human epidermal growth factor receptor 2 negative

Hormone receptor

Hormone receptor positive

Professional Society for Health Economics and Outcomes Research

Locally advanced breast cancer

Metastatic breast cancer

Medical Literature Analysis and Retrieval System Online

Medical subject headings

Mammalian target of rapamycin inhibitor

National Comprehensive Cancer Network

Newcastle Ottawa Scale

Objective response rate

Poly-ADP ribose polymerase inhibitor

Progression-free survival

Population, Intervention, Comparator, Outcome, Study Design

Partial response

Preferred Reporting Items for Systematic Literature Reviews and Meta-Analyses

Patient-reported outcomes

  • Real-world evidence

San Antonio Breast Cancer Symposium

  • Systematic literature review




United States

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The authors would like to acknowledge Joanna Bielecki who developed, conducted, and documented the database searches.

This study was funded by Pfizer Inc. (New York, NY, USA) and Arvinas (New Haven, CT, USA).

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Sarah Kane, Belal Howidi, Bao-Ngoc Nguyen and Imtiaz A. Samjoo contributed equally to this work.

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Sarah Kane, Belal Howidi, Bao-Ngoc Nguyen & Imtiaz A. Samjoo

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VL, IAS, SK, BH, BN, DC, YW, and ME participated in the conception and design of the study. IAS, SK, BH and BN contributed to the literature review, data collection, analysis, and interpretation of the data. VL, IAS, SK, BH, BN, DC, YW, and ME contributed to the interpretation of the data and critically reviewed for the importance of intellectual content for the work. VL, IAS, SK, BH, BN, DC, YW, and ME were responsible for drafting or reviewing the manuscript and for providing final approval. VL, IAS, SK, BH, BN, DC, YW, and ME meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work, and have given their approval for this version to be published.

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The authors of this manuscript declare that the research presented was funded by Pfizer Inc. and Arvinas. While the support from Pfizer Inc. and Arvinas was instrumental in facilitating this research, the authors affirm that their interpretation of the data and the content of this manuscript were conducted independently and without bias to maintain the transparency and integrity of the research. IAS, SK, BH, and BN are employees of EVERSANA, Canada, which was a paid consultant to Pfizer in connection with the development of this manuscript.

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Lambert, V., Kane, S., Howidi, B. et al. Systematic literature review of real-world evidence for treatments in HR+/HER2- second-line LABC/mBC after first-line treatment with CDK4/6i. BMC Cancer 24 , 631 (2024).

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An Integrative Review of Web 3.0 in Academic Libraries

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Purpose-The aim of this paper is to present an integrated literature review exploring the nature of responsive, semantic and interactive Web 3.0 technologies applicable for academic libraries. Design/methodology/approach-We conducted an integrated review of the literature combining a strategy of automated and keywords search. The main source for identifying the studies are Emerald Library Studies and Information & Knowledge Management eJournals, Web of Knowledge, and Library, Information Science & Technology Abstracts (EBSCO) databases. To this end, a sample of (n= 140) studies were analyzed to characterize the Web 3.0 trends and its applications based on theme, years and document types. Findings-A review of literature reveals that Web 3. needs evaluation as to what extent they are integrated, deployed and mainstreamed into library services and in information management practices. It is important to develop a conceptual framework that explores the linkages of Web 3.0 technologies and their applications in academic libraries. Originality/value-This review shows how Web 3.0 technologies enhance library services in its holistic conceptualization and how academic libraries are moving into a more robust, inclusive and adaptable phase in their service values and innovation.

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Sinonasal seromucinous hamartoma: a single institution case series combined with a narrative review of the literature

  • Published: 30 May 2024

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literature review on web 3 0

  • Chan Hee Kim   ORCID: 1 ,
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This study aimed to investigate the clinical and histopathological characteristics of sinonasal seromucinous hamartomas (SHs).

Eight patients with sinonasal SH and treated at a tertiary hospital between November 2005 and September 2023 were included. Additionally, a systematic review of published articles was conducted, analyzing 48 cases of SH described in the literature.

Among the eight patients treated at our institution, tumors originated from the posterior nasal cavity in four patients and middle turbinate and middle meatus were the primary origin in two patients each. Coexistence of inflammatory nasal polyps (NPs) was observed in four cases. Histopathologically, four patients exhibited focal respiratory epithelial adenomatoid hamartoma (REAH) features, and low-grade dysplasia was found in one patient. A combined analysis with previous literature revealed that 46.3% of all cases originated in the anterior nasal cavity. The proportions of cases accompanied by NPs and those with focal REAH features were 20.5% and 39.1%, respectively. Additionally, the frequencies of cases exhibiting dysplastic features (5.4%) and recurrence (2.1%) were low. Remarkably, tumors originating from the anterior region tended to have a higher frequency of dysplasia than those originating from the posterior region, although this difference was not statistically significant (p = 0.0996).

Patients with sinonasal SH showed favorable treatment outcomes following surgical resection. Focal REAH features and accompanying NPs were frequently observed. A substantial proportion of cases originate in the anterior nasal cavity, and these tumors may exhibit a high tendency for dysplasia.

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Sinonasal seromucinous hamartoma

literature review on web 3 0

Seromucinous Hamartoma of the Nasal Cavity

literature review on web 3 0

Nasal and sinonasal tumors formed by atypical adenomatous lesions arising in respiratory epithelial adenomatoid hamartoma/seromucinous hamartoma

Data availability.

The datasets analyzed during the current study are not publicly available due to ethical restrictions but are available from the corresponding author on reasonable request.

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This work was supported by the Basic Science Research Program through the NRF funded by the Ministry of Education (2021R1I1A1A01047571) and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI23C1464).

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Department of Otorhinolaryngology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea

Chan Hee Kim, Hyung-Ju Cho, Chang-Hoon Kim & Min-Seok Rha

The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Republic of Korea

Hyung-Ju Cho & Chang-Hoon Kim

The Korea Mouse Phenotyping Center, Yonsei University College of Medicine, Seoul, Republic of Korea

Chang-Hoon Kim

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Chan Hee Kim, conceptualization, methodology, investigation, formal analysis, writing—original draft. Hyung-Ju Cho, methodology, writing—review & editing. Chang-Hoon Kim, conceptualization, writing—review & editing. Min-Seok Rha, conceptualization, formal analysis, writing—review & editing.

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Correspondence to Min-Seok Rha .

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This study was performed in line with the principles of the Declaration of Helsinki. This study was approved by the Institutional Review Board of Severance hospital, Korea (IRB No. 4–2023-1183).

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Kim, C.H., Cho, HJ., Kim, CH. et al. Sinonasal seromucinous hamartoma: a single institution case series combined with a narrative review of the literature. Eur Arch Otorhinolaryngol (2024).

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Musk’s A.I. Firm Raises $6 Billion in Race With Rivals

Elon Musk, who founded xAI last year, has said the business “still has a lot of catching up to do” as it looks to compete with well-funded companies like OpenAI.

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Elon Musk wearing a black leather jacket and black pants and shirt stands in front of a poster of the PBS show “A Brief History of the Future.”

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Elon Musk’s artificial intelligence company, xAI, said on Sunday that it had raised $6 billion, helping to close the funding gap with OpenAI, Anthropic and other rivals in the red-hot industry.

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