The paper gives a detailed review of the approaches adopted for embedding information into/onto additively manufactured parts. The primary purpose of this paper is to review all the techniques adopted for embedding information, highlight notable trends and improvements in these works, and provide design and manufacturing pipelines to realize most of these works. It classifies these approaches into four different categories and summarizes the works carried out in each field. It also compares all the results in textual and tabular forms and then gives a detailed conclusion of the best works in terms of application and effectiveness. The four categories discussed are 3D QR codes, 3D watermarking, steganography and nonclassified methods. Lastly, it discusses the future extensions and potential improvements in the field of embedding information, while exploring manufacturing technologies. Over the years, there have been many notable developments in technology-related fields, ranging from conventional machining to computerized numerically controlled machining (CNC) and direct numerically controlled machines. The field of additive manufacturing (AM) known as 3D printing, in its pioneering stages, is a result of experiments carried out on numerous technologies. The advent of AM began in 1984 when a researcher named Charles Hull, later owner of 3D systems, filed a patent for layer-by-layer manufacturing. His work was recognized as one of the leading works in the field of additive manufacturing, which was followed by another patent filed by a researcher named Scott Crump in 1989, later known as the founder of Stratasys. The duration of the patent lasted for almost 20 years, during which 3D printers were not accessible to the public. In 2009, after the patent expired, an era of democratization of AM began, starting with the concept of rapid prototyping. This concept involved manufacturing models to test their fit, form and function requirements in various engineering fields. Further developments took place and resulted in the manufacturing of end products that were ready for use. Therefore, the name 3D printing finally received the name of additive manufacturing.Additive manufacturing, as the name implies, involves the addition of material layer-by-layer. It is exactly opposite to subtractive or machining methods and is based on volume modelling rather than the surface. A common generic AM process starts with the creation of a digital 3D model in a computer-aided design (CAD) environment. There are various CAD software tools facilitating the creation of 3D models. Once the model has been designed in the CAD environment, the 3D model file is converted into a format called stereolithography (STL), which approximates the surface of the model with triangle meshes containing the coordinates of the normal vectors and the vertices of the triangles. The STL format is the de facto standard, and there is a slow shift towards a file format with more advantages—the additive manufacturing file format (AMF). Once the file is converted into STL, it is loaded into the computer-aided manufacturing software (CAM) and slicing is carried out, producing machine codes. If these codes are generated within the CAD software directly, then it is known as direct slicing, and is preferable for complicated models. In the CAM software, numerous steps are taken such as setting the layer thickness, infill patterns, temperatures, power, supports and scaling, etc. Once these properties are outlined, a command to print is conveyed to the machine and the fabrication process starts. After the fabrication is completed, the part can be removed carefully, and the supports (if utilized) can be cleaned or dissolved, depending on the material used in the post-processing stage. The final part can then directly be put into use.The advent of AM proved to be advantageous for many reasons. It enables the manufacturing of complex geometries with ease and reduces the lead time as well. It significantly reduces the assembly steps and the cost of transportation due to remote production. It can also be used for several materials and avoids wastage. Internal channels can be developed easily and can be used for generative design, leading to mass reduction. Despite the advantages, numerous issues need to be worked out, such as the presence of porosity, mechanical strength issues and manufacturing time. However, with the continuous improvements taking place in the field of AM, it is a crucial part of the fourth industrial revolution.As mentioned in the paragraphs above, AM initially involves digital manufacturing using software such as CAD and CAM. AM is better put into practice when it is used for mass customization rather than mass production, because it enables the manufacturing of complex geometries and complicated products. Considering the initial stages of AM, there is significant potential for embedding information into/onto AM products, which can then be retrieved from the final fabricated models. The era of AM will have a remarkable impact on the future of manufacturing technologies, simultaneously opening different areas of research in this field. Information in the AM parts can be embedded in various forms and used for different purposes, ranging from object tracking to object authentication. Information embedded inside the AM part can also be used to make the AM part more interactive for the user. The focus of this paper is to explore major existing embedding technologies related to the AM parts and draw a comparison among them. The forms in which information is embedded onto/into AM parts can be divided into four major categories, namely QR codes, watermarking, steganography and other methods. The last category involves all those technologies presented and published that do not fall under the former categories.QR codes have been in use for a long time since their development, and major research has been carried out on their 2D forms. Taking a step further, a 3D QR code is generated if it is embedded onto/into AM part using different types of processes. This 3D QR code is easily scannable using a mobile device and does not get affected by wear and tear, as it is part of the product itself. This QR can be used for object authentication, tracking and monitoring purposes. This paper makes a comparison between different types of technologies involving 3D QR codes employing various AM technologies. Similarly, the concept of watermarking 3D content, such as videos and images, has been tested and applied for a long time; however, the advent of AM, involving digital manufacturing, created multiple problems for safeguarding copyrights. Therefore, to solve the copyright infringement issues, multiple technologies of watermarking 3D models  were proposed. This paper discusses all the major technologies related to embedding watermarks of 3D models and compares each of them in detail. A simple watermarking technique involves creating a watermark and embedding it inside the digital model. The model is fabricated, and cameras are used to scan and retrieve the watermark, hence protecting the original creators. Steganography, a term rarely used, is a technique of hiding information into/onto AM parts and retrieving it using a secret key. In this way, information can be conveyed to the end users without being leaked to the public. Different technologies involving steganography in 3D models are presented and compared. Specifically for this category, possible AM methods are mentioned in detail as well. The last category involves the usage of technologies in embedding information onto/into AM parts not belonging to the other three categories. These include works published to make the AM parts more interactive, such as integrating optical fibers, pressure sensors and air pockets. The following section gives a detailed overview of the structure of the paper and its layout.Considering the advent of AM around the globe, many 3D models have been created by various designers and manufacturers, from designing at a digital stage to achieving a fully functional physical product. This led to several avenues opening into different areas of research linked to the field of AM. One such avenue deals with embedding information onto/into additively manufactured products. Various approaches have been adopted to embed information and our paper aims to discuss these approaches and the works carried out in a detailed manner. This paper classifies the approaches into four main categories and focuses on the description and comparison of the techniques proposed in all four categories of embedding information onto/into AM parts.In the introductory part, the paper discusses the history of AM and different types of AM technologies linking their usage in the field of manufacturing. The second section is a thorough review of digital manufacturing linked with AM technology and the potential to embed information onto AM parts. This section discusses the four categories related to information embedding, along with their advantages. It starts with the 3D QR code approach, followed by watermarking 3D models, followed by steganography. Finally, it covers other information-embedding approaches. The subsections of this section discuss all the approaches employed in the field of embedding information into/onto AM parts. A basic pipeline, valid for each category, and the primary procedure are mentioned. Next, a table is given to compare all the AM-related properties of each work for each category. This table is further explained in detail and every paper is thoroughly discussed. The third section covers the future trends and applications perspective, highlighting the best work in each category while also pointing out the advantages of these technologies related to the fourth industrial revolution, as well as explicitly stating the scientific benefits. Finally, a concluding paragraph summarizes the paper and reiterates the main aim of this paper.This section includes a complete discussion of different works and technologies proposed in the field of embedding information into/onto AM parts. It draws comparisons between different works for each category and lists down their limitations and future extensions. Each section contains a table that compares different AM properties of the works proposed in each category. It starts with the QR technology being applied into/onto AM parts for various purposes, such as object authentication and tracking. In order to prevent copyright infringements issues, the next category describes the watermarking techniques for AM parts in detail. To hide the information and retrieve it, a technique called steganography is mentioned in the third category related to AM technologies. Similarly, the last category includes all the information-embedding methods in AM parts which do not fall in the upper three categories.Each QR code, as shown in The QR code, which originated in 1994, was developed by Masahiro Hara, who was an engineer at Denso Wave. Before QR codes, a common coding system in use for tagging and identifying the products was the barcode system. With the shift from a single product manufacturing to a flexible manufacturing systems and production, the need for storing more information while occupying less space became crucial. Therefore, experiments were carried out to increase the data storage capacity of the barcodes for better efficiency in the industry. However, due to certain limitations of the barcodes, such as storing 20 alphabetic characters and coding in traverse direction only, research for creating a 2D code started. After numerous efforts, Hara, along with their team of engineers, was able to come up with a 2D code that had 3 position detection patterns, making it easier to be read by scanners [The basic procedure followed in most of the techniques proposed in the literature, given in As with the first implementation, the concept of 3D QR code was proposed by Kikuchi et al. , who sugi et al.  marked tIn the same year as the previously mentioned study, a similar work was carried out by Chen et al. . Unlike A notable and novel QR-code-embedding approach was proposed by Wei et al.  using seIn addition to the fabrication of the metal parts with QR codes using various AM methods, consumer-level implementations were also accomplished. Yang et al.  proposedi et al. , this tei et al.  and Wei i et al. . MoreoveThere was another work in the field of embedding QR codes using self-shadows. Peng et al.  proposedi et al.  and Cheni et al. . It has There are other studies using the same technology (FFF) and the same material (PLA) to embed the QR codes onto the surface of AM parts. In one of these studies, Gultekin et al.  proposedFollowing the previously mentioned works, Peng et al.  introducus works ,5,6. It Compared with the previous works of Kikuchi et al.  and PengReviewing all the works carried out in this category of embedding information onto AM parts, the work of Kikuchi et al.  laid theComparing all the works, the most applicable, time-saving, and cost-effective solution was the work proposed by Papp et al. , specifiDigital watermarking is a technique used to prevent replication of the digital content and identify copyright infringement issues. It can be defined as a process which integrates digital data inside an object. With the growth of AM and an increase in the number 3D-printed parts, the need for digital watermarking has become more crucial in the recent years. Since AM begins with the design of 3D models in a CAD environment and ends with the fabrication on a 3D printing platform, the models produced can be reversed engineered easily and duplicates may cause a variety of copyright issues. Several watermarking techniques have been proposed over the years starting from embedding watermarks into the 3D meshes of a digital model to having watermarks inside the fabricated 3D objects. Watermarks can be divided into two types based on their perceptiveness—visible and invisible watermarks. The invisible watermarking technique can further be classified into spatial and transform-domain-based schemes, depending on the insertion space. Considering end applications, the watermarks are classified into two types, namely robust and fragile watermarking. Fragile watermarking involves the disappearance or changing of the watermark—once the object or the model is altered, it is invisible. The robust watermark remains inside the object or a model even though transformation attacks are carried out, such as scaling, rotating, filtering and resizing. The schematic in Yeo et al.  suggesteThe method of Yeo et al.  marked tTo prevent counterfeiting of products manufactured using AM, and checking their authenticity, Aliaga et al.  proposedOver the years, the techniques of watermarking have kept evolving at a fast pace. Another notable work was published by Suzuki et al. . They prMacq et al.  providedIn another work, Hou et al.  proposedTwo years later, Hou et al.  decided A notable method was proposed by Pham et al.  regardinPham et al.  further Similar research was carried out by Delmotte et al.  to embedPeng et al.  proposedLater, a notable technique was proposed by Delmotte et al. , in whicAs mentioned in the introductory paragraphs, the 3D printing process is controlled by a G-code file which dictates each step of the print process. To prevent security issues of copyright infringement and tampering of the G-code file, a self-embedding watermarking process is proposed by Li et al. . The proThe concept of watermarking 3D models began with the work of Yeo et al. . They weThe work carried out by Peng et al.  proved tSteganography can be defined as the art of hiding communication inside a medium. Over the years, the media used to hide communication evolved from tattoos and invisible inks to digital content, such as an image, a file or a video. Democratization of 3D printing opened a new avenue for storing and hiding communication and a vast amount of research was carried out. The basic method in a steganographic system starts with the identification of redundant bits of a cover medium. The redundant bits can be defined as the bits which can be altered or modified without disrupting the integrity of the medium. A model called the stego model is created by replacing the redundant bits with the hidden message data. It is important to highlight the difference between watermarking and steganography here, as both techniques fall under the category of hiding information. A watermarking technique is aimed to make the watermark impossible to be removed without affecting the quality of the object, hence the technique mostly focusing on the watermark is highly robust. On the other hand, steganography focuses on hiding information that can get destroyed even slight modifications take place in a stego medium. Regarding steganography, two important definitions should be kept in mind, namely capacity and security. Capacity refers to the amount of information that can be hidden in a medium, whereas security refers to the inability of the eavesdropper to decode the hidden communication . Figure The process starts with the creation of a model in a CAD environment. It is then approximated as a 3D triangle mesh and analyzed. Redundant bits are identified, and secret data is converted into a binary form using a key. Data are embedded inside the model in different ways depending on the technique employed. The model is later fabricated using a 3D printer and is then scanned using different 3D scanning techniques. The stego model is then analyzed for the hidden information and the communication is extracted using the same procedure of embedding but in reverse. The data obtained is in binary format which is then decrypted using a secret key.Cayre et al.  proposedAfter the work of Cayre et al. , Tsai etLater, Bogomjakov et al.  proposedIn the following year, Chao et al.  proposedLater, Yuan-Yu Tsai  proposedFollowing the work of Tsai , Kaveh eLater, Itier et al.  presenteAfter the work of Itier et al. , Li et aIn another study, Suzuki et al.  proposedThe main gap in employing steganography in the field of 3D models is the implementation of the algorithms on AM parts. Most of the research is carried out on 3D digital models and only few of them have been employed on 3D-fabricated physical models. It would be better to implement the techniques given above on real fabricated parts and check whether they can convey the information without disrupting the message hidden within them. Hence, major research is required in the field of steganography on fabricated AM parts.The concept of steganography was proposed by Cayre et al. in , in whicIn terms of the actual application of steganography on AM parts, the most suitable technique is the one proposed by Suzuki et al. . The reaThis section discusses different types of approaches developed over the years in the field of embedding information into/onto AM parts. All types of technologies mentioned here are completely different from the three categories discussed above and in no way share any similarity with them except for utilizing AM processes. The researchers embedded information inside the objects in various forms. These include embedding tags called infrastructs, which are based on materials and the information can be retrieved using Tetrahertz imaging. Moreover, this section also includes embedding of fiber optics to touch sensors making 3D parts more interactive, integrating AM parts with corrugated tubes and air pulses, forming fine cavities inside the AM parts representing information, embedding pictures inside the 3D parts, embedding tags for authentication and tracking purposes, and having different algorithms for detecting and extracting the embedded information. After the democratization of additive manufacturing, Willis et al.  proposedSimilarly, Hook et al.  proposedTo make the AM parts more interactive, Schmitz et al.  proposedLater, Stoll et al.  proposedThen, with the same goal of making AM parts more interactive, He et al.  proposedIn another study, Suzuki et al.  proposedLi et al.  proposedIn another approach, Nielsen et al.  decided Later, Tejada et al.  proposedThen, Maia et al.  proposedSilapasuphakornwong et al.  proposedFollowing this study, Silapasuphakornwong et al.  took theAnother different approach was proposed by Dogan et al.  on a tecLastly, Uyan et al.  proposedIn regards to embedding information onto AM parts, different techniques were proposed which did not fall under the three categories mentioned in the previous sections. In one of these studies , a technIt would be difficult to carry out an analysis to determine which technology is better than the rest, as all of them are built on separate concepts and algorithms. All these technologies aimed to embed information onto AM parts in one way or another. They were quite successful despite the limitations and proved to pave the way for more research in this field.The primary aim of embedding 3D QR codes started with product authentication and tracking. Regarding this, numerous works were published by notable researchers, which proved to be highly useful in accelerating the growth of 3D QR codes. Despite the numerous limitations of each work, as stated in the manuscript, they had specific future extensions other than the initial objectives. There were notable future trends that could be observed in 3D QR codes, as significant research can be conducted in exploring various techniques to minimize the scanning time and increase detection accuracy. The need for a background light for detection may be further minimized by exploring different embedding techniques. Various layer thicknesses and curved surfaces can be experimented upon to detect the maximum embedding depth, which is detectable using mobile phone scanners. Significant research is also required in the field of metal AM technologies. With the extensions of QR codes being embedded into metal parts, the metal industry can flourish, and the life cycle of the parts can quickly be recorded. In addition to the metal industry, different polymers of various colors can be employed to improve the detection ability without a contrasting background. A notable significant future extension could be increasing the range of scanning angles and obtaining the smallest possible size of a QR code using optimization procedures that are not affecting the strength of the products. An example benefit of such extensions could be the use of 3D QR codes on AM medicinal drugs, enabling the user to read the entire prescription method just by scanning them.In the field of watermarking, the primary aim of embedding these watermarks was to prevent the illegal distribution of the original products and to minimize the reverse engineering effects on the parts produced. There are specific extensions of the technologies produced in the field of watermarking aside from the detection of copyright infringement issues. The parts produced using PLA and ABS materials can be texted and experimented with different colors, and watermark information can be encrypted on the normals of triangular meshes. Moreover, using different AM technologies such as those dealing with metal manufacturing, such as BJ, SLM and DMLS, can be tested to make sure that the metal parts can easily be detected for their originality. Further refinement of watermarks can be carried out to make sure that the watermark is as invisible as possible and the mechanical properties of the manufactured parts are not affected due to their presence. One possible extension could be using a fully functioning scanning technology that detects and decreases the decryption time of watermarks. Various algorithms can be employed to make sure that the scanner detects the slightest variations or attacks on the originality of the part by observing changes in the watermarks. A significant extension includes the construction of the part while bringing as few changes as possible to the embedded watermark during the print and scan process. An all-in-one technology can be developed and distributed, which deals with embedding and detection of watermarks at low cost and consuming less time. This will prove to have extensive applications in the field of manufacturing and indirectly will relate to strengthening the global economies.The field of steganography is not new, and has been around for centuries employing different media. The main objective of employing steganography in the field of AM is to enable side-information channeling and tamper proofing of 3D models. Although the objectives of steganography and watermarking are similar, there are noticeable differences among them. One significant difference is the persistence of watermarks in the case of tampering. The main issue faced in this field of steganography is the amount of research and experiments carried out on the actual 3D models. Most of the algorithms available and the ones mentioned in this paper focus on digital 3D meshes. It is a known fact that during the fabrication and scan processes, the stego (code) hidden inside the model can get distorted, hence losing its ability to be decoded. There is a need for an optimized algorithm that can decrease the number of distortions taking place and increase the coding accuracy. The time required to decode the stego model and retrieve the hidden information can also be reduced. Point geometries inside the model can be explored for information hiding purposes, and better approximation and error criteria can be developed. The usage of steganography can further be expanded and integrated with Industry 4.0. Several types of information can be hidden in plain sight and detected using various mechanisms, thus proving beneficial for manufacturing and military industries, civil services, and political communication.The last category mainly describes the types of technologies employed in AM not belonging to the former three categories. Aside from using PLA and ABS, metal technologies can also be employed for embedding information into/onto AM parts. Different materials having different refractive indices can also be used and mixed with encoding and decoding data. In order to make the AM parts interactive, user feedback can be employed, and controls can be integrated inside the AM parts. One significant extension could be embedding braille patterns onto AM parts which will help the visually impaired people and can be extended to anything ranging from a key to a machine part. By embedding fiber electronics and tracking the mechanical health of the part, the structural integrity of the parts can be extended. Significant research is required in eliminating the requirements of supports and decreasing the resolution as low as possible. The algorithms can easily be automated to decrease the embedding and decoding times, making them time efficient and increasing the embedding capacity.The article highlights the notable works carried out and explores the scientific benefits and usage for each of them. The works carried out in the above mentioned categories can be linked with numerous scientific benefits and can be extended to various industries. A notable use of the QR code can be connected with the pharmaceutical industry in embedding prescriptions into medicinal drugs and tablets. With the help of bio-ink being used in additive manufacturing technology, simple tablets can have the whole prescription procedure written in them with the help of easily scannable QR codes. This will significantly decrease the side effects of improper usage of medicinal drugs and help in minimizing danger to human lives. With the developments in AM technologies and numerous companies working towards bio-friendly inks, inconsistencies with dental fixtures have been eased by employing Zirconia based brackets. By manufacturing these additively, numerous design problems related to human teeth can be solved, and the instruction of proper installation can be embedded inside these brackets using 3D QR codes. The use of watermarks in AM can play a pivotal role in tracing and tracking counterfeit products. This usage can be extended further when manufacturing human organs using bio-ink becomes a reality. A watermark can be embedded inside the human organ to assure its authenticity and can easily be tracked to its parent company with the help of scanning procedures. This way, illegal human organ trafficking can easily be curbed and stopped. Notable companies are working on building spheroids and 3D cell structures using various bio-printer assortments, and the dream of achieving a 3D-printed, fully functioning human organ is not far away. Once the technology is successfully developed, the usage of embedding watermarks can prove very beneficial to the medical industry and help further and prolong human lives. Aside from the medical sector, watermarks can be used in the automotive and aviation industry to detect the originality of the additively manufactured parts being used in the body of automobiles and aircraft. By lowering the number of counterfeit and faulty products, the number of human lives lost in accidents can be decreased. The art of steganography cannot only be used to detect counterfeit products but also in covert communication as well. By embedding information into additively manufactured parts, intelligence can be shared from one place to another secretly through means of different products. This can prevent intelligence leakage and can easily help maintain security problems around the globe. Using the technologies associated with embedding information into AM parts, the structural health of the part can be significantly monitored, thus help us determine the functioning part’s life cycle and prevent further damage to the entire machine.With the invention and development of several new polymers and other materials in additive manufacturing, the pace of work being carried out in the field of embedding information into/onto AM parts has accelerated. It is not surprising to associate these advancements as part of the fourth industrial revolution (Industry 4.0) as they are proving to be significantly valuable in industries and factories around the globe. The fourth industrial revolution deals with the innovations in controlling the industrial value chain and the idea of converging the real world with the virtual world to help achieve industrial smartness. The benefits of the industrial revolution not only include increased productivity but also encompass an increase in flexibility, quality and speed. With AM, the 3D printers and CAM software connected to the cloud open new areas in production, value creation and mass customization. Hence, with the inclusion of 3D printers, the factories related to manufacturing can be converted into smart factories with the ease of mass customization and bridging the physical and digital gap between the products. The concept of embedding information into/onto AM parts will significantly affect the entire value chain as it will enable tracking of the products from the beginning manufacturing to the final destination of the end customer. It will also decrease the authentication costs and simplify the tracking procedures. Moreover, it will also prove to have numerous benefits in protecting the copyrights and assuring genuineness. With the help of embedding information, be it QR codes, watermarking or steganography, personalized production will be heavily encouraged, simultaneously cutting down inefficiencies and intellectual theft and enhancing customer involvement with the manufactured parts. With the increase in customer involvement, customer loyalty will increase, which will result in the growth of innovation. By using cloud platforms, cutting-edge intelligence can be shared easily about the product as it can easily be tracked down to the manufacturer using the information embedded inside, while Industry 4.0 mainly focuses on mass production and customization with little human involvement, Industry 5.0 combines human and artificial intelligence in a workplace. However, this does not even begin to describe the benefits that it will bring to the manufacturing field. With the freedom of design responsibility given to humans, the boundaries of design will be pushed even further while 3D printers simultaneously work for manufacturing products. With the real-time data of the manufacturing product being transferred back to the designer, they can highlight better use of the product to the customer. This real-time data and usage information can be embedded inside the additively manufactured parts for the ease of the consumer, bringing considerable benefits to the future industries.This paper reviews significant technologies and works proposed for embedding information into/onto AM parts. It classifies these works into four categories: QR codes, watermarking for protecting copyrights, steganography (the art of hiding information), and other methods of embedding information on additively manufactured artifacts. All the categories are thoroughly discussed and compared. The best technique for each type is then selected for implementation while keeping various parameters in mind. The paper’s main aim is to emphasize the developments taking place at a rapid pace in the AM industry and highlight significant findings that will result in better improvements. These findings will further progress the fourth industrial revolution, simultaneously accelerating the global industries towards the fifth industrial revolution. All the technologies discussed above will rapidly improve industrial development and ensure the betterment of human lives.


Physical and Rehabilitation Medicine (PRM) is the medical specialty of body functioning. Its aim is to diagnose, prevent and reduce disability resulting from the interaction between people and their environment , 2.The World Health Organization (WHO) Global Disability Action Plan 2014–2021 “Better health for all people with disabilities” is a significant step toward rehabilitation services. For a successful implementation of the WHO recommendations, PRM organizations and individual PRM specialists are urged to contribute to the improvement of PRM services worldwide .The International Classification of Functioning, Disability and Health (ICF) provides a widely accepted conceptual model and taxonomy of human functioning .PRM specialists guarantee the citizen's access to rehabilitation services as a human right –6.It is well-known that rehabilitation is essential to lower healthcare costs by decreasing the number of days spent in hospital, and that reducing disability improves quality of life. Varela et al. highlight the need for more scientific studies on the benefits of rehabilitation even in the preoperative phase, while we know that current studies confirm that early postoperative rehabilitation decreases pain and its consequences .In long-term disabilities, the rehabilitation process for patients with complex problems requires a carefully planned and integrated program by the PRM physician who provides advice on diagnosis, prognosis, treatment options and risks for the patient and family. The PRM physician must take his leadership role over the rehabilitation team, as well as assist in the development of treatment protocols; his holistic perspective on long-term rehabilitation management makes a unique contribution .High-quality rehabilitation care is a constituent element of healthcare systems worldwide. The implementation of these standards needs to be validated worldwide with particular attention to low- and middle-income countries. The standardization of staff training at both undergraduate and postgraduate levels is a key element in ensuring the highest standard of rehabilitation care. International bodies, such as the UEMS Board for PRM or the International Society for PRM, have already delivered normative documents setting standards in postgraduate PRM training.They highlight the need to develop competency-based education, training physicians with the proper skills and knowledge required to meet the healthcare needs of people with disabilities, as a powerful mechanism to align education and training with health system priorities.This is of particular value for countries with limited resources, where the knowledge and skills of rehabilitation physicians need to reflect not only the health profile of the population, but also the strengths and weaknesses of the health system.As life expectancy increases, disability rates caused by the diseases listed above increase , 10.The World Disability Report published by WHO in 2011 also states that the prevalence of severe and moderate disability is higher in Africa than in many other regions of the world especially in younger (<60 years) population groups , 13.A number of publications report a prevalence of disability in the general population ranging from 1.7% in Mali  to 17.1%Disability prevalence in Cameroon was recently estimated in a survey of a sample of 1,617 adults aged 18+ using the Washington Group tools, which capture self-reported activity limitations in functional domains described in the ICF . There aA study in a health district in Cameroon showed that many disabilities, such as orthopedic problems (mainly fractures), infectious diseases and neurological disabilities , were due to traffic accidents and inappropriate medical interventions . In MaliA large number of studies explored the effect of disability on health, education, social participation and livelihoods of people with disabilities.Adults with disabilities were more likely to experience serious health problems and report limited access to healthcare and rehabilitation services .A literature review published in 2018 on five West African countries defined important policy and program implications as follows:(1) Application of standardized tools for monitoring the implementation of programs and policies at national level;(2) Improving stakeholder coordination mechanisms at the country level;(3) Supporting countries in using unified approaches to measuring disability and social exclusion;(4) Strengthening the rigor of the evaluations of the effectiveness of disability-specific interventions;(5) Disaggregation of routine data from development programs by disability .A disability research team established the need to define strategies to improve the activities of daily living of people with disabilities in Cameroon .A descriptive cross-sectional study pointed out that disabled people, and children in particular, are still marginalized, vulnerable and with little chance of recovery. Therefore, there is a clear need to improve the quality and availability of rehabilitative care with programmatic interventions that improve the accessibility to rehabilitation services for people with disabilities, provide them with the necessary safeguards, ensure implementation of existing laws, and neutralize any barrier to their social participation .Regarding disability associated with human immunodeficiency virus (HIV) infection, a 2019 study shows that antiretroviral therapy improves impaired immune function. It is reported in the literature that physical (aerobic/endurance) exercises also seem to induce beneficial effects .In another 2019 study, Ibeneme et al. argue that while aerobic exercise does not improve levels of inflammatory biomarkers (IL-6 and IL-1β), it does significantly improve cardiopulmonary function in HIV-infected patients .The importance of rehabilitation medicine is also evident from a 2019 literature review on HIV-infected children with impairments and disabilities. Unfortunately, we know that pediatric health systems in Sub-Saharan Africa are not integrated with rehabilitation in chronic diseases such as HIV while integration to pediatric Rehabilitation in a holistic approach would be important. This scoping review proposes a synthesis of existing evidence on rehabilitation intervention strategies for disability-related barriers in children living in Sub-Saharan Africa .The incidence of diabetes mellitus (DM) in Africa is not only a health problem but also imposes a significant economic burden. Diabetic peripheral neuropathy is a common microvascular complication of DM that increases the potential for morbidity and disability due to ulceration and amputation. Based on the study analysis, the highest prevalence of diabetic peripheral neuropathy in patients with DM was reported in West Africa at 49.4%. The need for a rehabilitation medicine approach also has its importance here .Despite concerns about underreporting of cerebral palsy (CP) in many African communities, the prevalence estimates reported here were generally higher than the estimated 2–2.5 of 1,000 in most studies conducted in the United States or Europe . It is lThere is a paucity of studies in Africa, South-East Asia and the Eastern Mediterranean region on pulmonary diseases, with increasing prevalence of chronic obstructive pulmonary disease, both globally and regionally .In the same way patients with idiopathic pulmonary fibrosis (IPF) generally experience poor quality of life. A study reports that these patients are poorly referred to palliative care even in developed countries, while in developing countries no data are available on the use of palliative care or the burden of health care management. Therefore, more awareness and research on the palliative care needs of patients with IPF is recommended, particularly in resource-limited settings such as South Africa .About the burden of stroke in Africa, the results of a review suggest that is high and still rising. The incidence of stroke in Africa is becoming a public health challenge; unfortunately scarcity of data has limited research and consequently also the response to the exact public health burden.In 2019, a total of 1.89 million stroke survivors were estimated among people aged 15 years or older in Africa. There is a need for extensive research on both stroke and other vascular risk factors to institute appropriate policy, and effective preventive and management measures .Regarding the rheumatologic diseases, a systematic review identified the paucity of latest prevalence data on arthritis in Africa .After this excursus of the most important diseases that afflict the African continent, this systematic review of the empirical literature, from 2016, emphasizes the importance of exploring the sustainability of health interventions in Sub-Saharan Africa.From the analysis of these studies, we can define the importance of rehabilitation and the need for more studies in this area .For the application of proper rehabilitation in the field of PRM, a study emphasizes the need to understand the current learning styles of physiotherapy students and if necessary also change the teaching styles in order to provide high quality education. Currently, physiotherapy students have specific learning styles of active participation supported by practical internship activities and theoretical concepts. Further research would be fundamental to define and standardize learning styles in physiotherapy courses .The results of a study published in 2009 offer the first global portrait of the dynamics of demand and supply of human resources for rehabilitation: the lowest supply of rehabilitation health professionals was found among low- and middle-income countries, many located in Sub-Saharan Africa, where the burden of cause-related diseases requiring rehabilitation professional skills tends to be greatest. Worldwide, people with disabilities have many unmet health and rehabilitation needs but continue to face significant barriers in accessing mainstream health services, and consequently have poorer health outcomes. Currently, a double burden is found in low- and middle-income countries. Unfortunately, human resources for rehabilitation are often a neglected component of health services .In light of what has been examined so far, we discuss the current situation of disability and PRM in the Cameroon healthcare system and their possible perspectives.Healthcare system promotes equity in people. In addition, WHO reported that people with disabilities are also entitled to attain the best possible quality of care without discrimination. In the same vein, Cameroon has signed and ratified numerous national and international conventions on disability with the aim to attain a number of privileges for disabled persons, which have been recently characterized by Foti et al. . It is iRehabilitation aims to optimize functional ability, enhance quality of life and reduce disability in people with impaired health conditions through interventions. According to the WHO, countries with the lowest levels of health (and education) fail to sustain real growth and development , 36. AreThe current Cameroon medical system woefully underprepares clinicians to efficiently prescribe exercise-based rehabilitation. In addition, the majority of fellowships offer no training in exercise prescriptions. In Cameroon, the PRM curricula are not available in the existing medical schools. However, general physiotherapy and/or rehabilitation, speech therapy, occupational therapy, orthoprosthesis and psychomotricity programs are offered by some universities and institutions in Cameroon as elective teaching modules. Therefore, PRM as a medical specialty is not well-known.Curriculum is an initial step for the development of any field and guide health research. In Cameroon, research in the field of rehabilitation also suffers. Thus, we propose some following points for a call to action to implement and disseminate this impactful discipline in Cameroon:(1) Develop a 4-year higher specialty training program in PRM;(2) Gain recognition of the new specialty in Cameroon by the Ministry of Higher Education;(3) Establish a system such as training and research in rehabilitation to ensure continuity competence of physicians practicing PRM in Cameroon, according to recommendations and standards provided by international PRM boards: “To acquire the wide field of competence needed, specialists in Physical and Rehabilitation Medicine have to undergo a well-organized and appropriately structured training of adequate duration. In fact they are required to develop not only medical knowledge, but also competence in patient care, specific procedural skills, and attitudes toward interpersonal relationship and communication, profound understanding of the main principles of medical ethics and public health, ability to apply policies of care and prevention for disabled people, capacity to master strategies for reintegration of disabled people into society, apply principles of quality assurance and promote a practice-based continuous professional development” , 38.We can confirm that high-quality rehabilitation care is essential within health systems, especially for low- and middle-income countries. The importance of adapting staff training both at university and post-graduate level is a fundamental element to ensure the highest standard of rehabilitation care.The review carried out on the literature relating to the main diseases that cause disabilities in Africa with particular regard to Cameroon highlighted shortcomings in the health systems both at a social and welfare level; for this reason, the aim is to define training courses and strategies that can guarantee the best level training to provide better intervention systems for professionals in PRM. This is why the international bodies of PRM highlight the need to develop training that allows education to be aligned with the priorities of the health system.As regards Cameroon, a fundamental aspect would be to recognize the specialization in PRM by the Ministry of Higher Education, developing a 3 or 4-year educational program and improving scientific research in this field.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.Publication of article was funded by Chair of Physical Medicine and Rehabilitation, Clinical Sciences and Translational Medicine Department, Tor Vergata University, Rome, Italy.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Shared decision-making (SDM) is particularly important in oncology as many treatments involve serious side effects, and treatment decisions involve a trade-off between benefits and risks. However, the implementation of SDM in oncology care is challenging, and clinicians state that it is difficult to apply SDM in their actual workplace. Training clinicians is known to be an effective means of improving SDM but is considered time consuming.This study aims to address the effectiveness of an individual SDM training program using the concept of deliberate practice.This multicenter, single-blinded randomized clinical trial will be performed at 12 Dutch hospitals. Clinicians involved in decisions with oncology patients will be invited to participate in the study and allocated to the control or intervention group. All clinicians will record 3 decision-making processes with 3 different oncology patients. Clinicians in the intervention group will receive the following SDM intervention: completing e-learning, reflecting on feedback reports, performing a self-assessment and defining 1 to 3 personal learning questions, and participating in face-to-face coaching. Clinicians in the control group will not receive the SDM intervention until the end of the study. The primary outcome will be the extent to which clinicians involve their patients in the decision-making process, as scored using the Observing Patient Involvement–5 instrument. As secondary outcomes, patients will rate their perceived involvement in decision-making, and the duration of the consultations will be registered. All participating clinicians and their patients will receive information about the study and complete an informed consent form beforehand.This trial was retrospectively registered on August 03, 2021. Approval for the study was obtained from the ethical review board . Recruitment and data collection procedures are ongoing and are expected to be completed by July 2022; we plan to complete data analyses by December 2022. As of February 2022, a total of 12 hospitals have been recruited to participate in the study, and 30 clinicians have started the SDM training program.This theory-based and blended approach will increase our knowledge of effective and feasible training methods for clinicians in the field of SDM. The intervention will be tailored to the context of individual clinicians and will target the knowledge, attitude, and skills of clinicians. The patients will also be involved in the design and implementation of the study.Netherlands Trial Registry NL9647; https://www.trialregister.nl/trial/9647DERR1-10.2196/35543 Shared decision-making (SDM) has been promoted to support patients in making informed decisions that best fit their personal preferences, circumstances, and concerns ,2. This Fighting cancer is paramount in the focus of both clinicians and patients, which may impede the process of considering multiple treatment options and weighing their short- and long-term consequences ). Data will be entered by the study coordinator (LJP).Ethical approval for the study was obtained in December 2020, and thereafter, until December 2021, each of the 12 participating hospitals obtained local approval for this study. The first clinician started with the individual SDM training program in May 2021. As of February 2022, we enrolled 30 clinicians, of whom 5 (17%) have completed the training program. The pace of participant inclusion in the study is increasing; therefore, study recruitment is planned to be finalized around July 2022. We plan to complete data analyses by December 2022.A mixed cofunding was obtained from the participating clinicians themselves (voluntary contribution), from the Dutch OncoZon-Citrienfonds , CZ Health Care Insurer, and DSW-Phoenix Health Care Insurer.The study results will be disseminated to partnering organizations, study participants, and organizations involved in the development of clinician education. The findings will be submitted to a peer-reviewed journal and presented at academic conferences.We hypothesize that clinicians exposed to this intervention are more likely to adopt SDM behavior than clinicians who do not, resulting in decisions that better match the preferences and values of oncology patients. We expect that clinicians in the intervention group will increase their observed level of SDM after each part of the intervention. We also believe that the effect of the training program will be at least as large as the average increase that other interventions have shown . AnotherWe have previously worked on designing effective interventions, including training, to help clinicians adopt SDM in daily practice ,31,32. TA strength of our approach is that it will be tailored to the context of individual clinicians and that it targets attitudes, knowledge, and skills of clinicians. The possible limitation of this protocol could be that participating clinicians may already have an inclination toward SDM, which can lead to selection bias. Therefore, we will try to invite clinical teams rather than individuals to participate in this study to include a group of clinicians with a wide range of SDM interests and skills. Another limitation is that the clinicians cannot be blinded to the intervention. This might encourage them to practice SDM apart from the intervention itself.This trial takes the next step in the pursuit of developing effective training methods for clinicians in the field of SDM. It will increase our knowledge about how effective and feasible the direct observation of audio-recorded health care encounters, followed by constructive feedback from a coach, can be. Principles of deliberate practice are used as the basis for the educational approach, which enables effective learning , and theOur intervention incorporates important elements from the theory of deliberate practice, such as having a well-defined goal, motivation to improve, and providing feedback on real-life situations . NeverthFor most patients with cancer, multiple treatment options exist, and SDM is crucial to support them in making informed decisions that best fit their personal preferences. Clinicians play an important role in enhancing SDM implementation; however, SDM implementation remains challenging. This study will examine the effectiveness of an individual SDM training program for physicians. The results of this study will be disseminated through publication in an open-access journal to enable the uptake of this deliberate practice study in other fields of interest and through presentations. In the Netherlands, patient organizations, professional bodies, and health care insurers are involved in the project and are committed to using valuable results for daily practice. Although our educational intervention is a mixed set of interventions with several elements over a 10-week period, it is relatively short and labor intensive, with one-on-one feedback and coaching. For implementation, it is important to take this into account and continue to look for interventions that are applicable in daily  care as well as support a continuous learning process for clinicians.


To analyze the anxiety, depression, and related factors among pregnant women with cervical insufficiency, so as to provide a reference for clinical psychological intervention as an adjuvant therapy.A total of 101 cases in China with cervical insufficiency were included in the observation group by a convenience sampling method, and 114 normal healthy women of childbearing age were selected as the control group. Participants were investigated and observed for anxiety and depression by SAS and SDS, respectively, to analyze the emotional state and influencing factors of the patients with cervical insufficiency. Stratified by the first, second and third trimesters, our study used whether depressive or not and whether anxiety or not as the dichotomous variables. A multivariate Logistic regression was adopted to analyze the influencing factors. Relevant influencing factors were screened out by the forward stepwise method in combination with professional knowledge and the number of variables.There were statistical significant differences in SAS and SDS between observation group and control group and the incidence rate of anxiety and depression was higher in pregnant women with CI. Multivariate Logistic regression demonstrated that history of abnormal pregnancy was the main influencing factor for anxiety and depression in the early and middle gestation phases, and cervical insufficiency was the factor influencing the anxiety in early gestation and both anxiety and depression in the late gestation phase.Cervical insufficiency may have a negative impact on the emotions of pregnant women. Individualized and targeted mental care should be added into clinic work to prevent negative outcomes. Cervical insufficiency (CI) refers to an anatomical or functional abnormality causing progressive and painless shortened, dilated, flattened, and funneled cervix before full-term pregnancy, which may lead to the inability to maintain pregnancy in the 2nd and 3rd trimesters. CI accounts for about 1% of all pregnancies and it is an important reason for recurrent abortion and premature delivery in the 2nd and 3rd trimesters .By now, several surgical methods have been proposed for the treatment of CI worldwide, including transvaginal and transabdominal cervical cerclages, in which the latter can be done by open or laparoscopic surgery , 5. Yao During the pregnancy period, women would obtain greatly change not only in their physiological, but also their psychological state. Previously studies demonstrated that up to 11.9% of pregnancy women could be diagnosis as depression state , meanwhiAs we mentioned above, patients with CI may have several times of unwilling spontaneous abortion between 16 and 28 weeks. Study have shown that unwilling pregnancy termination before 28 weeks of gestation, which often happen in patients suffered from CI, could lead to adverse mental health consequences . Since wIn our study, we tried to explore the emotional state of patients with CI at different gestation phases and relevant influencing factors for the first time in China, so as to provide specific health education for pregnant women with CI, improve their psychological state, promote maternal and child safety, and provide valuable reference for clinical intervention and nursing.A total of 101 pregnant women diagnosed as CI in the First Affiliated Hospital of Sun Yat-sen University  between May 2019 and December 2020 were included as the observation group by a convenient sampling method, and 114 healthy women of childbearing age were included as the control group. Inclusion criteria for the observation group: ① Patients with definite CI; ② Patients who received laparoscopic cervical cerclage during early pregnancy in our hospital; ③ Patients with intrauterine pregnancy confirmed by B-ultrasonography, gestational weeks ≤15; ④ Those understanding the investigation and willing to cooperate; ⑤ With live fetus confirmed before surgery. Based on a principle of randomness and equilibrium, 114 healthy pregnant women in the same period were included as the control group. Inclusion criteria for the control group: ① Healthy women of childbearing age, aged 18–49 years; ② Pregnant women without chronic diseases and pregnancy-related complications;③ Those voluntarily cooperating with the investigators. Women who meet the following exclusion criteria will not be included: (1) People with mental retardation that may affect their understanding for the questionnaires; (2) People with history of mental illness and malignant tumor; (3) Those taking antipsychotic drugs during pregnancy; (4) Those with genetic diseases. In strict accordance with the inclusion and exclusion criteria and following the consent of the ethics committee, 116 CI patients signed on the informed consent, and 101 were finally included as observation group according to the criteria.There was a psychological questionnaire during pregnancy, which was composed of general information and scales for psychological testing of anxiety and depression. The questionnaire survey is conducted by a face-to-face interview for the investigators collecting relevant data one by one. After the investigators answer the questionnaire in detail, the assessed subjects fill in the questionnaire independently. The subjects completed the questionnaires independently after the investigators explained in detail, and then, the investigators collected the questionnaires and check them one by one, so as to guarantee the authenticity and validity of the survey results.All participants were fully informed and agreed to participate in this study. Written informed consent was obtained from all of the participants.Self-rating Anxiety Scale (SAS)  and SelfP < 0.05, there was statistical significance for relevant difference. The internal consistency of current study data of SDS and SAS was calculated using SPSS20.0, and the result was α = 0.875.Stratified by the first, second and third trimesters, our study used whether depressive or not and whether anxiety or not as the dichotomous variables. A multivariate Logistic regression was adopted to analyze the influencing factors. Relevant influencing factors were screened out by the forward stepwise method in combination with professional knowledge and the number of variables. The SPSS20.0 software was used for relevant statistical analysis. If This study has been approved by the Ethics Committee of the First Affiliated Hospital of Sun Yat-sen Medical University, approval number: Lunzhen (2020) No. 178.The demographic data of the included patients are as shown in P < 0.05). Meanwhile, no matter mild, moderately or severely anxiety and depression, we noticed the incidence rate was significantly increased in CI group from As shown in As shown in Muyiduli et al.  and BuneThis study found that among pregnant women with CI, history of abnormal pregnancy or delivery was the main factor influencing the anxiety and depression in the first and second trimesters, and CI was the factor influencing the anxiety in the first trimester as well as the anxiety and depression in the third trimester. CI may cause poor pregnancy outcomes, and history of repeated abortion in the 2nd trimester of pregnancy may cause endless harm to both the pregnant women and their families . AccordiBased on the characteristics of psychological conditions of the pregnant women with CI in different trimesters, an initial targeted intervention was carried out. We established a We Chat group named as “Sun Yat-sen - Circle of Life”, and arranged professional doctors to answer relevant questions and conduct health education in the group, so as to relieve the anxiety and depression of relevant women during pregnancy. However, this study is merely based on the authors' experience in remote education , and relPreviously researches didn't investigate the depression and anxiety situation in pregnancy women with cervical insufficiency. For the first time in the world, our study focus on the depression and anxiety in those patients after cervical cerclage, which can provide more helps on the care of this group. In addition, this article provides the knowledge of psychological nursing in pregnancy women with cervical insufficiency, which helps to prevent adverse pregnancy outcomes.This study also has some limitations as follows: 1. Asthe self-rating scale was adopted in this study, unavoidable bias may occur since the subjectivity of the respondents. In future, examiner-rating scales should be used for further evaluation. 2. In this study, only patients with CI in the First Affiliated Hospital of Sun Yat-sen University from China were included, and so, the conclusion is to be further verified by multi-center studies.In conclusion, for the first time in the world, this study explored the emotional problems of pregnant women with CI. CI may affect the emotions of pregnant women, and poor psychological states may threaten the maternal and infant health in China. Individualized and targeted mental care should be added into clinic work to prevent negative outcomes. Further research can improve the credibility of research results by expanding the sample size and adopting more objective scales for evaluation.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.The studies involving human participants were reviewed and approved by the First Affiliated Hospital of Sun Yat-sen University. The patients/participants provided their written informed consent to participate in this study.FW and JC were responsible for management and oversight of the study. QW and QZ were responsible for general omnibus data analyses and were keys contributing authors to the manuscript. CL and GH were responsible for all research interviews and clinical chart reviews associated with this study. XZ and YZ provided guidance on the design of primary analyses. YY assisted with all data collection, analysis, and writing of the manuscript. All authors contributed to the study design and data interpretation and critically reviewed the manuscript and gave final approval for its publication.This work was supported by grants from the National Natural Science Foundation of China (No. 31771074), the Science and Technology Plan Project of Guangdong (No. 2019B030316001), the Program of Guangzhou (No. 201807010064), and the Science and Technology Plan of Xizang (No. XZ2019ZRG-152).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Atrial functional regurgitation is caused by atrioventricular annulus dilation, with normal leaflets and ventricular dimensions and function within the normal range. Its occurrence, in both mitral and tricuspid valves, implies a worse prognosis due to the hemodynamic derangement they produce, but also constitutes a marker of greater comorbidity and more advanced disease. Predisposing conditions for these heart valve dysfunctions are mainly atrial fibrillation and heart failure with preserved ejection fraction. However, other factors like female sex also may be involved and influence their incidence, especially for atrial tricuspid regurgitation. In the present review, we analyze sex differences in the reported prevalence of atrial mitral and tricuspid regurgitation, and suggest possible mechanisms involved. Finally, we underline potential therapeutic and preventive strategies to reduce the burden of these heart valve disorders and discuss research gaps. Secondary regurgitation of atrioventricular valves is characterized by geometric changes of the valvular apparatus secondary to dilation and/or dysfunction of the ventricles or atria. In contrast to primary atrioventricular regurgitation, the leaflets of the mitral and tricuspid valves are structurally normal. Accordingly, the management of secondary atrioventricular valve regurgitation differs significantly from that of primary regurgitation since it needs to target the underlying mechanism first rather than fixing directly the anatomy and competence of the atrioventricular valve . SecondaWhile it is well known that women with AF and/or HFpEF (which are associated with AMR and ATR) present at a more advanced course of the disease as compared to men and the implementation of the available therapies may differ between the two sexes , 19, thep < 0.001)  . In an a< 0.001) –27.When analyzing the frequency of AMR from the underlying pathophysiology point of view, the sex differences are less clear. A substudy of the Atherosclerosis Risk in Communities (ARIC) Study investigating the association between AF and mitral regurgitation among patients hospitalized for acute decompensated heart failure showed that among 9,104 patients with HFpEF, 2,501 had significant mitral regurgitation and 4,437 had AF. Although the mechanism of mitral regurgitation was not specified, most probably the majority of the patients had AMR since patients with primary mitral regurgitation would have been excluded as per study design. The proportion of female was comparable among patients with and without AF  and the frequency of AF increased with increasing severity of mitral regurgitation . Therefop < 0.001) (p < 0.001) but not in men  (p < 0.001), LA dilation and increasing pulmonary artery systolic pressure  . It was  < 0.87) . This wapressure . Regardipressure .The possible causes for the higher proportion of women with AMR and ATR as compared to men are not completely understood and remain speculative. First, some studies point to distinct factors that may lead to more advanced LA dysfunction and more atrial fibrosis in women than in men , higher As a result of this higher susceptibility of women for this type of atrioventricular valve regurgitation as compared to men, strategies aimed at reducing the occurrence of AMR and ATR may have a greater impact in women than in men. The development of AMR and ATR has been associated to worse prognosis, as it entails volume overload and decreased stroke volume, but also because they are both markers of more advanced atrial remodeling due to increased AF burden, diastolic dysfunction, LA failure and pulmonary hypertension. Therefore, early diagnosis and adequate treatment of related conditions may impact on the burden of AMR and ATR, particularly in women. For instance, it is acknowledged that women with AF are diagnosed later and received less rhythm control as compared to men, as demonstrated in the EORP-AF Pilot survey . SubsequThe use of new percutaneous transcatheter therapies may increase in the future for the treatment of symptomatic and refractory significant AMR  and ATR There is currently a growing interest in the field of AMR and ATR due to their increasing prevalence, prognostic implications and novel therapeutic strategies. In this regard, research on sex differences in pathophysiology, clinical presentation and treatment approach is warranted and could help to better understand these heart valve diseases. On the other hand, a closer attention is required to prevent sex inequity in diagnosis and treatment of AF and HFpEF , 60, 61,AMR and ATR occur mainly in patients with AF and HFpEF and are associated with higher rates of heart failure and mortality. Observational data demonstrate a higher prevalence of these heart valve diseases in women, especially for ATR. Mechanisms involved in this sex distribution are not well-understood, and may be related to differences in histopathological characteristics of the atrio-ventricular annuli and leaflets and different time-course or treatment strategies of the predisposing conditions in women compared to men. Research gaps include pathophysiological determinants and unbiased incidence of both heart valve diseases, as well as differential treatment strategies. Awareness of these sex-related differences from the clinical ground to the echocardiography laboratories and the investigational setting may contribute to improve the knowledge and better management of these valve disorders in both sexes.FG-C and VD contributed to the conception and design of the paper. FG-C drafted the manuscript. JS, AB-G, and VD contributed to the critical revision of the manuscript. All authors contributed to the article and approved the submitted version.VD received speaker fees from Abbott Vascular, Edwards Lifesciences, GE healthcare, Medtronic, MSD and Novartis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


By leveraging the recent development of artificial intelligence algorithms, several medical sectors have benefited from using automatic segmentation tools from bioimaging to segment anatomical structures. Segmentation of the musculoskeletal system is key for studying alterations in anatomical tissue and supporting medical interventions. The clinical use of such tools requires an understanding of the proper method for interpreting data and evaluating their performance. The current systematic review aims to present the common bottlenecks for musculoskeletal structures analysis  and the related strategies utilized by different authors. A search was performed using the PUBMED database with the following keywords: deep learning, musculoskeletal system, segmentation. A total of 140 articles published up until February 2022 were obtained and analyzed according to the PRISMA framework in terms of anatomical structures, bioimaging techniques, pre/post-processing operations, training/validation/testing subset creation, network architecture, loss functions, performance indicators and so on. Several common trends emerged from this survey; however, the different methods need to be compared and discussed based on each specific case study . These findings can be used to guide clinicians (as end users) to better understand the potential benefits and limitations of these tools. In recent years, several deep learning tools have been implemented for the segmentation of anatomical structures to support a wide range of clinical applications for rapid and high-precision evaluation. Deep learning tools for the segmentation of the musculoskeletal system have been proposed to assist clinicians with applications in the field of computer-assisted surgery ,2; the fImage segmentation is a process used to simplify the representation and analysis of an image and it consists of the classification of pixels to localize and delineate the shape of the objects represented ,18. The The term neural network is derived from neuroscience and these algorithms mimic the brain mechanism, that is, the brain is a gigantic network of neurons and the neural network is a network of nodes . A varieThe use of deep learning segmentation algorithms for medical applications needs to be discussed based on the computational strategies implemented for their development. In this way, the clinician, as an end user, does not obtain false interpretations of the results. For this reason, the aim of this investigation was to analyze the current state-of-the-art solutions for segmentation, with a focus on musculoskeletal structures, using deep learning approaches. The novelty of this work is to provide clinical experts with an overview of the challenges that have been faced in previous studies in the literature and the related solutions that have been implemented to develop an automated artificial intelligence tool that is capable of investigating (segmenting) musculoskeletal structures from bioimages and designed to meet today’s clinical needs. These results contribute to our understanding of the limits and advantages of the use of such tools in clinical practice.The results of this systematic review were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) . A searcIn general, deep learning models are trained/validated/tested using two elements: a set of labeled data (annotated images recognized as ground truth/gold standard) and a neural network architecture that contain many layers .Starting with the pipeline of a generic deep learning tool for the segmentation of musculoskeletal structures from medical images, the purpose of this section is to present the main challenges and the related solutions that have been implemented in the literature for tool development.The literature shows that deep learning algorithms have been developed for different imaging modalities for the segmentation of a variety of musculoskeletal structures. In terms of anatomical structures, we found solutions for the following: 33% were related to the lower limbs , 8% to the upper limbs , 34% to the trunk , 3% pelvis , 14% to the head , and 8% to the whole body . Concerning medical imaging, 39% of the studies used magnetic resonance imaging (MRI), 9% used ultrasonography (US), 41% used computed tomography (CT), 9% used X-ray, and 2% used pluri-imaging modalities see .In relation to the imaging modality, the main difficulties are attributed to factors such as variable image contrast, the inherent heterogeneity of the image intensity, image artifacts due to motion, spatial resolution  ,87. TherBioimaging “mining” for clinical purposes could be extremely powerful under certain circumstances that rely on raw data acquisition, selection and processing, to solve bottlenecks such as a small sample size and data inhomogeneity.The success of any deep learning approach is highly dependent on the availability of a quality dataset (of labeled images) to train the network by using many samples (“big data”) . Then, oThe risk in training a network with a small set of data is that it can degenerate into an overfitting problem, when a significant gap between training and testing error occurs and the network is extremely sensitive to small changes in data representation.Data augmentation, which consists of artificially increasing the number of training samples, is commonly implemented to solve the problem of overfitting and to boot network efficiency. The choice of its implementation is very context-specific. In this survey, data augmentation was performed by approximately half of the authors, and most of the time this involved applying various image processing techniques  to the dataset see . Other rTo manage small sample datasets, another solution is the transfer learning technique, which was implemented in more than 10% of the analyzed papers. The aim of transfer learning is to make a pre-existing algorithm reusable for a new dataset since it consists of using a pre-trained network , and customizing it to the specific segmentation task so that the algorithm will only learn specific features for the new data   see Tab.One of the biggest problems related to building the database is that the data often comes from different hospitals, it has been acquired with different devices, it has different resolutions/noises/illumination, and lacks repeatability; thus, the data includes large variations among different subjects/the same subjects monitored at different times, and therefore the dataset must be pre-processed ,108. In More than half of the authors (57%) implemented a pre-processing phase before the deep learning training step. The most commonly implemented pre-processing techniques were normalization; histogram equalization, which is used to increase the contrast of the image by spreading its intensity values; and intensity-based/dimensional-based filtering see .Meanwhile, cropping and resizing methods (downsizing) were generally used to save memory space and are fundamental to match the dimensional requirements of the network input. When the region of interest (foreground) is small in relation to the background, then operations  do not preserve the informative content of the tissue, thus leading to the loss of object details and surrounding relative contextual data. Instead, a two-pass run is a potential solution, where the native image should be processed in the first pass to allow the network to learn other significant determinants that may not be detected in the pre-processed one  see Tab.As reported by Klein et al. in 2019 , sometimThere are several strategies that are applied for the splitting of training/validation/testing subsets from the ground truth collection. In general, a training set is used for model training and construction, a validation set is used to monitor the model training process and observe the training effects, a test set is used to assess the generalization capabilities of the model . In the As reported by Goodfellow et al. 2016 , one proA bottleneck that should be considered in both of the abovementioned methods, is the redundancy in the data content. Redundant information can occur, for example, in the case of patients with multiple scans or images where the background is more prevalent compared to the foreground . The latIn addition to the above considerations, to acquire representative subsets, Ackermans et al. 2021  suggesteThe segmentation of anatomical structures can be performed based on the availability of bioimaging datasets through 2D or 3D approaches; however, combining the benefits of both solutions remains a challenge. The main reason the 2D method is popular is that it does not require an oversized dataset  and it is also very economical in terms of its computational and memory requirements. However, a 2D method does not fully utilize all sequence information . This limitation could be overcome by using a 3D network capable of improving the continuity of the sequential slices and better segmentation of the small parts of the organs ,113.As trade-off strategies, the models could be trained by alternating the input batches by using batches of different planes  in such a way that the network learns to segment structures independent of the viewing direction, as proposed by Klein et al. 2019 . AlternaIn fact, over the years, various network architectures have been developed to segment musculoskeletal structures. One of the most popular models of the convolutional neural network (CNN), a type of artificial neural network that is widely used in the imaging domain, is the U-Net graph in its original form as proposed by Ronneberger et al. 2015  or a modHowever, the choice of network architecture is driven by the case under study, which could guide the implementation of a new ad hoc design with a customized structure, as chosen by Kuang et al. 2020 .To further improve the segmentation capability of the network, one design architecture strategy that could be considered is the introduction of an attention module, as proposed in ,39. AtteOnce the dataset and the network architecture have been defined, then the network should be trained/validated and tested to evaluate its performance through the use of different score indices.In supervised learning, network training is the process where the segmented images, as the net output, are compared with a group of labeled images, as the net input, until the convergence between input and output is obtained (as error reduction). In other words, supervision means that each input image is coupled with a label, and this association is learned from the network to predict a specific output. During the learning process, the network weights are updated to reduce the error between the experts’ annotation (ground truth/labeled images) and the network prediction. This error is then evaluated and quantified through validation and testing processes. According to the concepts discussed in the previous sections regarding data labeling and weights update, To reduce the burden of manual pixel-level annotations, so-called “weak” supervision has also attracted significant interest since, as explained by Kervadec et al. 2019 , it consDuring the training process, the difference between the expected output and the predicted one is estimated by the loss function. The training loss is used to update the weights and biases, while the validation loss determines whether the learning rate parameter  is lowered or the training is stopped . In factThe most common loss functions used by the papers reported in this survey were the DICE function or variants (27%), cross entropy or variants (23%), or a combination of both (7%), see Comparing different deep learning architectures is a difficult task, and a network performance that is comparable to human observers could be considered a strong indicator of practical clinical utility . HoweverThus, to validate the process, it is important to compare the selected technique with manual segmentation and with other network architectures. The most used indices to quantify network performance in terms of the overlap between ground truth and network predictions were the DICE index (DSC) (85%), Intersection over Union (IoU or Jaccard Index) (30%), Hausdorff distance (HD) (18%), and surface distance (SD) (18%). The HD and SD indices are generally used in case of 3D model reconstruction from multiple slices segmentation see .Another way to quantify the network performance is the run time of the predictions since it is crucial for the clinical real-time applicability of the tool. As evaluated by Ackermans et al. 2021 , the segAn additional drawback in terms of timing efforts, is the tuning of the network hyperparameters (parameters set by users to control the learning process), which is performed for model optimization (such as the previously mentioned learning rate). This operation can be done based on a grid search or random search process , e.g., bNonetheless, some authors have highlighted that network convergence could also be influenced by factors not strictly related to software or hardware development, such as the clinical conditions of patients under evaluation. For example, as demonstrated by Hemke et al. 2020 , a variaAfter the abovementioned steps, different post-processing strategies could be implemented to ensure a more accurate outcome, to improve consistency, to refine the predictions, and correct mislabeling errors. Different post-processing techniques were selected by 18% of the surveyed authors for segmentation refinement  see .In any case, after the segmentation process, it is crucial to restore the properties of the original image, both in terms of resizing and resolution, as neural networks generally work with square matrices.Starting with the pipeline of a generic deep learning tool for the segmentation of musculoskeletal structures from medical images, the purpose of this systematic review was to offer a quick overview to clinical experts of the solutions proposed in the literature to fulfill the segmentation task, and to better clarify the potentiality and limitations in the usage of similar tools to complement their daily practices.The results demonstrated that several solutions have been proposed in recent years for the segmentation of musculoskeletal structures for a variety of body parts  with different bioimaging modalities  for clinical application, where automation is key to reduce the human effort involved in manual annotations (which are time consuming and prone to errors). Such tools should perform reliable and fast object characterization through a user-friendly interface, reduce costs and contribute to large-scale clinical process management and scale-up.Tool feasibility relies, on a case-by-case basis, on its application, the anatomical structure to be analyzed and the bioimaging technique used for the investigation. The training/validation/testing of segmentation algorithms on non-public and single-institution datasets makes the comparison with published results infeasible due to the different conditions—in terms of the quantity of test images, the imaging parameters and hardware, the pathological status (or none) of the patients, and so on . TherefoThe comparison between different methods has to be discussed on the basis of each specific case study ; however, some common trends emerged from this investigation. These included the network architecture , loss function , post-processing refinement  and outcome indicators  to evaluate the goodness of predictions.Bottlenecks such as small sample size, data inhomogeneity and imprecise segmentation could be solved by data augmentation and pre- and post-processing operations, respectively, but the impact of such computational solutions should be considered in regard to the results to avoid false interpretations. Moreover, the accuracy of the predictions of an algorithm is a meaningful quantity not only when obtaining high values but also when the network learning process has been properly designed, with training as exhaustive as possible in regard to the variance of real cases, as encountered in daily practice.Deep learning is a widely used solution due to its ability to learn the useful representation of an object from a bioimage in a self-learned way and without prior super-imposition of user-designed features . For instance, this is the reason why vertebra segmentation relies on the integrity of intervertebral discs and is limited in the case of disc disease. In other words, a thoracic vertebra is identified not only due to its intrinsic features, but also due to the fact that it lies close to a disc (the disc is an extrinsic feature for vertebra that becomes a “landmark for the network” in this specific case of backbone segmentation). This also explains the limitation incurred when using patch-based approaches, where only limited contextual information is extracted and concur with outcomes predictions. Thus, the deep learning paradigm allows us to simultaneously investigate multiple pieces of information from an input, and to understand the way they are integrated and mutually influenced by each other. Therefore, network learning from huge amounts of data might suggest new biomarkers as predictors of musculoskeletal diseases through bioimaging analysis .A “deep” knowledge of the workflow for tool development could support the evaluation of current or new software solutions for clinical applications, where the paradigm of the “patient at the center” requires tailored analysis and optimized settings. A segmentation tool could potentially increase the effectiveness of a physical therapy  if it could perform real-time parameter tuning, precisely based on each specific scenario and the conditions of the musculoskeletal structure, thus focusing the intervention on the precise level of the altered structure itself. In practice, a similar deep learning segmentation tool could help to guide clinicians in a customized investigation of the structures potentially implicated in a specific condition, in planning the best intervention, in re-evaluating treatments’ effectiveness and in monitoring their follow up.The purpose of the current survey was to provide clinicians with a quick overview of the milestones for developing deep learning tools and to understand their applicability.The challenge of this type of research was to overcome the problem of the different nomenclatures used by different authors to define the same topic, to identify common strategic solutions  and report the relative percentages (if significant).The limitations of this type of research include the focus on the analysis on the musculoskeletal system and on the segmentation tasks. Further research could be conducted on other systems and tasks such as classification.The search could also be extended to other topics such as network optimization  and publicly available databases for network training/validation/testing.Future work could also include numerical statistics (in terms of performance indicators resulting from different tools) and the definition of a rating scale that compares different items .In conclusion, the clinical application of deep learning tools for musculoskeletal structure segmentation should be considered in the light of the strategies implemented for their development, to correctly explain their outcomes and evaluate their implications in the clinical domain. The availability of deep learning modules, integrated in medical devices for the segmentation of musculoskeletal structures could hasten and refine the precision of the treatment with the evolution of tailored devices, thus reducing human error and improving patient quality of life, while offering a new perspective of interpretability in the medical imaging domain and moving towards new frontiers in medical care.